Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Panza E, De Cicco P, Armogida C, Scognamiglio G, Gigantino V, Botti G, Germano D, Napolitano M, Papapetropoulos A, Bucci M, Cirino G, Ianaro A. Role of the cystathionineγlyase/hydrogen sulfide pathway in human melanoma progression. Pigment Cell Melanoma Res 2014;28:61-72. [DOI: 10.1111/pcmr.12312] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Accepted: 08/26/2014] [Indexed: 12/21/2022]

For:	Panza E, De Cicco P, Armogida C, Scognamiglio G, Gigantino V, Botti G, Germano D, Napolitano M, Papapetropoulos A, Bucci M, Cirino G, Ianaro A. Role of the cystathionineγlyase/hydrogen sulfide pathway in human melanoma progression. Pigment Cell Melanoma Res 2014;28:61-72. [DOI: 10.1111/pcmr.12312] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Accepted: 08/26/2014] [Indexed: 12/21/2022]

Number

Cited by Other Article(s)

Birg A, Lin HC. The Role of Bacteria-Derived Hydrogen Sulfide in Multiple Axes of Disease. Int J Mol Sci 2025;26:3340. [PMID: 40244174 PMCID: PMC11990059 DOI: 10.3390/ijms26073340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 03/27/2025] [Accepted: 03/27/2025] [Indexed: 04/18/2025] Open

Guo Z, Xiao Y, Wu W, Zhe M, Yu P, Shakya S, Li Z, Xing F. Metal-organic framework-based smart stimuli-responsive drug delivery systems for cancer therapy: advances, challenges, and future perspectives. J Nanobiotechnology 2025;23:157. [PMID: 40022098 PMCID: PMC11871784 DOI: 10.1186/s12951-025-03252-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Accepted: 02/18/2025] [Indexed: 03/03/2025] Open

Borbényi-Galambos K, Erdélyi K, Ditrói T, Jurányi EP, Szántó N, Szatmári R, Czikora Á, Schmidt EE, Garai D, Cserepes M, Liszkay G, Tóth E, Tóvári J, Nagy P. Realigned transsulfuration drives BRAF-V600E-targeted therapy resistance in melanoma. Cell Metab 2025:S1550-4131(25)00021-X. [PMID: 40037361 DOI: 10.1016/j.cmet.2025.01.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 12/13/2024] [Accepted: 01/22/2025] [Indexed: 03/06/2025]

Affiliation(s)

Klaudia Borbényi-Galambos Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hajdú-Bihar County, 4032, Hungary
Katalin Erdélyi Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary
Tamás Ditrói Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary
Eszter Petra Jurányi Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary; Semmelweis University Doctoral School, Semmelweis University, Budapest, 1094, Hungary
Noémi Szántó Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary
Réka Szatmári Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hajdú-Bihar County, 4032, Hungary; Chemistry Coordinating Institute, University of Debrecen, Debrecen, Hajdú-Bihar County, 4012, Hungary
Ágnes Czikora Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary
Edward E Schmidt Department of Anatomy and Histology, HUN-REN-UVMB Laboratory of Redox Biology, University of Veterinary Medicine, Budapest, 1078, Hungary; Department of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, 59717, United States of America
Dorottya Garai Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hajdú-Bihar County, 4032, Hungary
Mihály Cserepes Department of Experimental Pharmacology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary
Gabriella Liszkay Department of Dermatology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary
Erika Tóth Department of Surgical and Molecular Pathology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary
József Tóvári Department of Experimental Pharmacology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary
Péter Nagy Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, 1122, Hungary; Chemistry Coordinating Institute, University of Debrecen, Debrecen, Hajdú-Bihar County, 4012, Hungary; Department of Anatomy and Histology, HUN-REN-UVMB Laboratory of Redox Biology, University of Veterinary Medicine, Budapest, 1078, Hungary.

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Zhang R, Shi W, Wu X, Yu Q, Xiao Y. Application of hydrogen sulfide donor conjugates in different diseases. Nitric Oxide 2025;154:128-139. [PMID: 39662602 DOI: 10.1016/j.niox.2024.11.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 07/05/2024] [Accepted: 11/19/2024] [Indexed: 12/13/2024]

Dawoud A, Youness RA, Elsayed K, Nafae H, Allam H, Saad HA, Bourquin C, Szabo C, Abdel-Kader R, Gad MZ. Emerging roles of hydrogen sulfide-metabolizing enzymes in cancer. Redox Rep 2024;29:2437338. [PMID: 39643979 PMCID: PMC11626870 DOI: 10.1080/13510002.2024.2437338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2024] Open

Zhu Z, Ma X, Liu X, Zheng L, Zhang L, Dai X, Li H, Zhang Z, Wang B, Huang X, Ge J, Ren Q. CBS/CSE mediated H₂S production induced AMPs expression through Toll pathway in crabs with black gill syndrome. FISH & SHELLFISH IMMUNOLOGY 2024;154:109965. [PMID: 39401741 DOI: 10.1016/j.fsi.2024.109965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 09/19/2024] [Accepted: 10/11/2024] [Indexed: 10/17/2024]

Affiliation(s)

Ziyue Zhu Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, 210023, Jiangsu Province, China
Xingkong Ma Freshwater Fisheries Research Institute of Jiangsu Province, Nanjing, Jiangsu Province, 210017, China
Xiaohan Liu Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, 210023, Jiangsu Province, China
Liangmin Zheng Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, 210023, Jiangsu Province, China
Lihua Zhang Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, 210023, Jiangsu Province, China
Xiaoling Dai Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, 210023, Jiangsu Province, China
Hao Li Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, 210023, Jiangsu Province, China
Zhaoqian Zhang Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, 210023, Jiangsu Province, China
Bingyan Wang Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, 210023, Jiangsu Province, China
Xin Huang Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, College of Marine Science and Engineering, Nanjing Normal University, Nanjing, 210023, Jiangsu Province, China.
Jiachun Ge Freshwater Fisheries Research Institute of Jiangsu Province, Nanjing, Jiangsu Province, 210017, China.
Qian Ren School of Marine Sciences, Nanjing University of Information Science and Technology, Nanjing, 210044, Jiangsu Province, China.

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Relouw S, Dugbartey GJ, McLeod P, Knier NN, Santiesteban FM, Foster PJ, Cadieux-Pitre HA, Hague NM, Caine J, Belletti K, Major S, O'Neil C, Gabril MY, Moussa M, Huynh MJ, Haeryfar SMM, Sener A. Pharmacological Inhibition of Endogenous Hydrogen Sulfide Production Slows Bladder Cancer Progression in an Intravesical Murine Model. Pharmaceuticals (Basel) 2024;17:1212. [PMID: 39338373 PMCID: PMC11435360 DOI: 10.3390/ph17091212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/06/2024] [Accepted: 09/13/2024] [Indexed: 09/30/2024] Open

Abstract

Present bladder cancer therapies have relatively limited therapeutic impact and account for one of the highest lifetime treatment costs per patient. Therefore, there is an urgent need to explore novel and optimized treatment strategies. The present study investigated the effects of inhibiting endogenous hydrogen sulfide (H2S) production on bladder cell viability and in vivo tumor progression. We targeted the H2S-producing enzyme, cystathionine γ-lyase, in 5637 cells using propargylglycine (H2S inhibitor) and performed cytofluorimetric analysis to evaluate cell viability. We then tested the efficacy of propargylglycine alone or in combination with gemcitabine (conventional chemotherapy) in an intravesical murine model of bladder cancer. Magnetic resonance imaging and immunohistochemical staining for cell proliferation, apoptosis, immune-cell infiltration, and neovascularization were performed to evaluate tumor response. Compared to control conditions or cohorts, propargylglycine administration significantly attenuated bladder cancer cell viability in vitro (p < 0.0001) and tumor growth (p < 0.002) and invasion in vivo. Furthermore, propargylglycine enhanced the anti-cancer effects of gemcitabine, resulting in tumor regression (p < 0.0001). Moreover, propargylglycine induced cleaved PARP-1-activated apoptosis (p < 0.05), as well as intratumoral CD8+ T cell (p < 0.05) and F4/80+ macrophage (p < 0.002) infiltration. Propargylglycine also reduced intratumoral neovascularization (p < 0.0001) and cell proliferation (p < 0.0002). Importantly, the pro-apoptotic and anti-neovascularization effects of gemcitabine were enhanced by propargylglycine co-administration. Our findings suggest that inhibition of endogenous H2S production can be protective against bladder cancer by enhancing the chemotherapeutic action of gemcitabine and may be a novel pharmacological target and approach for improved bladder cancer diagnosis and treatments in the future.

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Affiliation(s)

Sydney Relouw Department of Microbiology & Immunology, Western University, London, ON N6A 5C1, Canada Matthew Mailing Center for Translational Transplant Studies, Western University, London Health Sciences Center, London, ON N6A 5A5, Canada
George J Dugbartey Matthew Mailing Center for Translational Transplant Studies, Western University, London Health Sciences Center, London, ON N6A 5A5, Canada Department of Surgery, Western University, London, ON N6A 5C1, Canada Department of Pharmacology & Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra P.O. Box LG43, Ghana Department of Physiology & Pharmacology, Accra College of Medicine, East Legon, Accra P.O. Box CT9828, Ghana
Patrick McLeod Matthew Mailing Center for Translational Transplant Studies, Western University, London Health Sciences Center, London, ON N6A 5A5, Canada
Natasha N Knier Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada Robarts Research Institute, Western University, London, ON N6A 3K7, Canada
Francisco Martinez Santiesteban Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada
Paula J Foster Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada Robarts Research Institute, Western University, London, ON N6A 3K7, Canada
Heather-Anne Cadieux-Pitre Department of Animal Care & Veterinary Services, Western University, London, ON N6A 5C1, Canada
Nicole M Hague Department of Animal Care & Veterinary Services, Western University, London, ON N6A 5C1, Canada
Jenna Caine Department of Animal Care & Veterinary Services, Western University, London, ON N6A 5C1, Canada
Kaitlin Belletti Department of Animal Care & Veterinary Services, Western University, London, ON N6A 5C1, Canada
Sally Major Matthew Mailing Center for Translational Transplant Studies, Western University, London Health Sciences Center, London, ON N6A 5A5, Canada Department of Animal Care & Veterinary Services, Western University, London, ON N6A 5C1, Canada
Caroline O'Neil Robarts Research Institute, Western University, London, ON N6A 3K7, Canada
Manal Y Gabril Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 5C1, Canada
Madeleine Moussa Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 5C1, Canada
Melissa J Huynh Department of Surgery, Western University, London, ON N6A 5C1, Canada Lawson Health Research Institute, London, ON N6C 2R5, Canada
S M Mansour Haeryfar Department of Microbiology & Immunology, Western University, London, ON N6A 5C1, Canada Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada Lawson Health Research Institute, London, ON N6C 2R5, Canada Department of Medicine, Division of Clinical Immunology & Allergy, Western University, London, ON N6A 5C1, Canada Department of Oncology, Western University, London, ON N6A 5C1, Canada
Alp Sener Department of Microbiology & Immunology, Western University, London, ON N6A 5C1, Canada Matthew Mailing Center for Translational Transplant Studies, Western University, London Health Sciences Center, London, ON N6A 5A5, Canada Department of Surgery, Western University, London, ON N6A 5C1, Canada Lawson Health Research Institute, London, ON N6C 2R5, Canada

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Liang XY, Wang Y, Zhu YW, Zhang YX, Yuan H, Liu YF, Jin YQ, Gao W, Ren ZG, Ji XY, Wu DD. Role of hydrogen sulfide in dermatological diseases. Nitric Oxide 2024;150:18-26. [PMID: 38971520 DOI: 10.1016/j.niox.2024.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 06/30/2024] [Accepted: 07/04/2024] [Indexed: 07/08/2024]

Affiliation(s)

Xiao-Yi Liang Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China
Yan Wang Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China
Yi-Wen Zhu School of Clinical Medicine, Henan University, Kaifeng, Henan, 475004, China
Yan-Xia Zhang Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China
Hang Yuan Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China
Ya-Fang Liu Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China
Yu-Qing Jin Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China
Wei Gao Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China
Zhi-Guang Ren Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China; Kaifeng Key Laboratory of Infectious Diseases and Biosafety, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.
Xin-Ying Ji Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China; Kaifeng Key Laboratory of Infectious Diseases and Biosafety, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China; Faculty of Basic Medical Subjects, Shu-Qing Medical College of Zhengzhou, Zhengzhou, Henan 450064, China.
Dong-Dong Wu Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China; Kaifeng Key Laboratory of Infectious Diseases and Biosafety, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China; Department of Stomatology, Huaihe Hospital of Henan University, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China.

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Gao W, Liu YF, Zhang YX, Wang Y, Jin YQ, Yuan H, Liang XY, Ji XY, Jiang QY, Wu DD. The potential role of hydrogen sulfide in cancer cell apoptosis. Cell Death Discov 2024;10:114. [PMID: 38448410 PMCID: PMC10917771 DOI: 10.1038/s41420-024-01868-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 02/05/2024] [Accepted: 02/14/2024] [Indexed: 03/08/2024] Open

Affiliation(s)

Wei Gao Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China
Ya-Fang Liu Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China
Yan-Xia Zhang Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China
Yan Wang Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China
Yu-Qing Jin Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China
Hang Yuan Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China
Xiao-Yi Liang Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China
Xin-Ying Ji Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China. Faculty of Basic Medical Subjects, Shu-Qing Medical College of Zhengzhou, Zhengzhou, Henan, 450064, China.
Qi-Ying Jiang Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.
Dong-Dong Wu Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China. School of Stomatology, Henan University, Kaifeng, Henan, 475004, China. Department of Stomatology, Huaihe Hospital of Henan University, Kaifeng, Henan, 475000, China.

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Song YH, Lei HX, Yu D, Zhu H, Hao MZ, Cui RH, Meng XS, Sheng XH, Zhang L. Endogenous chemicals guard health through inhibiting ferroptotic cell death. Biofactors 2024;50:266-293. [PMID: 38059412 DOI: 10.1002/biof.2015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 10/17/2023] [Indexed: 12/08/2023]

Affiliation(s)

Yuan-Hao Song College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan, China
Hong-Xu Lei Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China Department of Chemistry, University of Chinese Academy of Sciences, Beijing, China
Dou Yu Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China
Hao Zhu College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan, China
Meng-Zhu Hao College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan, China
Rong-Hua Cui College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan, China
Xiang-Shuai Meng College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan, China
Xie-Huang Sheng College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan, China
Lei Zhang Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Tissue Engineering Laboratory, Jinan, China Department of Radiology, Shandong First Medical University, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China

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Zineldeen DH, Mushtaq M, Haider KH. Cellular preconditioning and mesenchymal stem cell ferroptosis. World J Stem Cells 2024;16:64-69. [PMID: 38455100 PMCID: PMC10915960 DOI: 10.4252/wjsc.v16.i2.64] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 01/04/2024] [Accepted: 01/19/2024] [Indexed: 02/26/2024] Open

Youness RA, Habashy DA, Khater N, Elsayed K, Dawoud A, Hakim S, Nafea H, Bourquin C, Abdel-Kader RM, Gad MZ. Role of Hydrogen Sulfide in Oncological and Non-Oncological Disorders and Its Regulation by Non-Coding RNAs: A Comprehensive Review. Noncoding RNA 2024;10:7. [PMID: 38250807 PMCID: PMC10801522 DOI: 10.3390/ncrna10010007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 01/07/2024] [Accepted: 01/08/2024] [Indexed: 01/23/2024] Open

Hipólito A, Mendes C, Martins F, Lemos I, Francisco I, Cunha F, Almodôvar T, Albuquerque C, Gonçalves LG, Bonifácio VDB, Vicente JB, Serpa J. H₂S-Synthesizing Enzymes Are Putative Determinants in Lung Cancer Management toward Personalized Medicine. Antioxidants (Basel) 2023;13:51. [PMID: 38247476 PMCID: PMC10812562 DOI: 10.3390/antiox13010051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 12/24/2023] [Accepted: 12/26/2023] [Indexed: 01/23/2024] Open

Affiliation(s)

Ana Hipólito iNOVA4Health, NOVA Medical School, 1150-069 Lisbon, Portugal; (A.H.); (C.M.); (F.M.); (I.L.) Molecular Pathobiology Research Unit, fromThe Portuguese Institute of Oncology (IPOLFG), 1099-023 Lisbon, Portugal; (I.F.); (C.A.)
Cindy Mendes iNOVA4Health, NOVA Medical School, 1150-069 Lisbon, Portugal; (A.H.); (C.M.); (F.M.); (I.L.) Molecular Pathobiology Research Unit, fromThe Portuguese Institute of Oncology (IPOLFG), 1099-023 Lisbon, Portugal; (I.F.); (C.A.)
Filipa Martins iNOVA4Health, NOVA Medical School, 1150-069 Lisbon, Portugal; (A.H.); (C.M.); (F.M.); (I.L.) Molecular Pathobiology Research Unit, fromThe Portuguese Institute of Oncology (IPOLFG), 1099-023 Lisbon, Portugal; (I.F.); (C.A.)
Isabel Lemos iNOVA4Health, NOVA Medical School, 1150-069 Lisbon, Portugal; (A.H.); (C.M.); (F.M.); (I.L.) Molecular Pathobiology Research Unit, fromThe Portuguese Institute of Oncology (IPOLFG), 1099-023 Lisbon, Portugal; (I.F.); (C.A.)
Inês Francisco Molecular Pathobiology Research Unit, fromThe Portuguese Institute of Oncology (IPOLFG), 1099-023 Lisbon, Portugal; (I.F.); (C.A.)
Fernando Cunha Pathology Department, The Portuguese Institute of Oncology (IPOLFG), 1099-023 Lisbon, Portugal;
Teresa Almodôvar Pneumology Department, The Portuguese Institute of Oncology (IPOLFG), 1099-023 Lisbon, Portugal;
Cristina Albuquerque Molecular Pathobiology Research Unit, fromThe Portuguese Institute of Oncology (IPOLFG), 1099-023 Lisbon, Portugal; (I.F.); (C.A.)
Luís G. Gonçalves Institute of Chemical and Biological Technology António Xavier (ITQB NOVA), 2780-157 Oeiras, Portugal; (L.G.G.); (J.B.V.)
Vasco D. B. Bonifácio IBB-Institute for Bioengineering and Biosciences, Associate Laboratory i4HB-Institute for Health and Bioeconomy, IST-Lisbon University, 1049-001 Lisbon, Portugal; Bioengineering Department, IST-Lisbon University, 1049-001 Lisbon, Portugal
João B. Vicente Institute of Chemical and Biological Technology António Xavier (ITQB NOVA), 2780-157 Oeiras, Portugal; (L.G.G.); (J.B.V.)
Jacinta Serpa iNOVA4Health, NOVA Medical School, 1150-069 Lisbon, Portugal; (A.H.); (C.M.); (F.M.); (I.L.) Molecular Pathobiology Research Unit, fromThe Portuguese Institute of Oncology (IPOLFG), 1099-023 Lisbon, Portugal; (I.F.); (C.A.)

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Martelli A, d'Emmanuele di Villa Bianca R, Cirino G, Sorrentino R, Calderone V, Bucci M. Hydrogen sulfide and sulfaceutic or sulfanutraceutic agents: Classification, differences and relevance in preclinical and clinical studies. Pharmacol Res 2023;196:106947. [PMID: 37797660 DOI: 10.1016/j.phrs.2023.106947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 10/01/2023] [Accepted: 10/02/2023] [Indexed: 10/07/2023]

Nafea H, Youness RA, Dawoud A, Khater N, Manie T, Abdel-Kader R, Bourquin C, Szabo C, Gad MZ. Dual targeting of H₂S synthesizing enzymes; cystathionine β-synthase and cystathionine γ-lyase by miR-939-5p effectively curbs triple negative breast cancer. Heliyon 2023;9:e21063. [PMID: 37916110 PMCID: PMC10616356 DOI: 10.1016/j.heliyon.2023.e21063] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 10/08/2023] [Accepted: 10/13/2023] [Indexed: 11/03/2023] Open

Abstract

Introduction

Hydrogen sulfide (H2S) has been recently scrutinized for its critical role in aggravating breast cancer (BC) tumorigenicity. Several cancers aberrantly express H2S synthesizing enzymes; Cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). However, their levels and interdependence in BC require further studies.

Objectives

Firstly, this study aimed to demonstrate a comparative expression profile of H2S synthesizing enzymes in BC vs normal tissue. Moreover, to investigate the reciprocal relationship between CBS and CSE and highlight the importance of dual targeting. Finally, to search for a valid dual repressor of the H2S synthesizing enzymes that could cease H2S production and reduce TNBC pathogenicity.

Methods

Pairwise analysis of tumor vs. normal tissues of 40 BC patients was carried out. The TNBC cell line MDA-MB-231 was transfected with oligonucleotides to study the H2S mediated molecular mechanisms. In silico screening was performed to identify dual regulator(s) for CBS and CSE. Gene expression analysis was performed using qRT-PCR and was confirmed on protein level using Western blot. TNBC hallmarks were evaluated using MTT, migration, and clonogenicity assays. H2S levels were detected using a AzMc fluorescent probe.

Results

BC tissues exhibited elevated levels of both CBS and CSE. Interestingly, upon CBS knockdown, CSE levels increased compensating for H2S production in TNBC cells, underlining the importance of dually targeting both enzymes in TNBC. In silico screening suggested miR-939-5p as a regulator of both CBS and CSE with high binding scores. Low expression levels of miR-939-5p were found in BC tissues, especially the aggressive subtypes. Ectopic expression of miR-939-5p significantly repressed CBS and CSE transcript and protein levels, diminished H2S production and attenuated TNBC hallmarks. Moreover, it improved the immune surveillance potency of TNBC cells through up regulating the NKG2D ligands, MICB and ULBP2 and reducing the immune suppressive cytokine IL-10.

Conclusion

This study sheds light on the reciprocal relationship between CBS and CSE and on the importance of their dual targeting, particularly in TNBC. It also postulates miR-939-5p as a potent dual repressor for CBS and CSE overcoming their redundancy in H2S production, a mechanism that can potentially attenuate TNBC oncogenicity and improves the immunogenic response.

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Oza PP, Kashfi K. The Triple Crown: NO, CO, and H₂S in cancer cell biology. Pharmacol Ther 2023;249:108502. [PMID: 37517510 PMCID: PMC10529678 DOI: 10.1016/j.pharmthera.2023.108502] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 07/16/2023] [Accepted: 07/19/2023] [Indexed: 08/01/2023]

Kalkan H, Panza E, Pagano E, Ercolano G, Moriello C, Piscitelli F, Sztretye M, Capasso R, Di Marzo V, Iannotti FA. Dysfunctional endocannabinoid CB1 receptor expression and signaling contribute to skeletal muscle cell toxicity induced by simvastatin. Cell Death Dis 2023;14:544. [PMID: 37612317 PMCID: PMC10447569 DOI: 10.1038/s41419-023-06080-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 08/05/2023] [Accepted: 08/16/2023] [Indexed: 08/25/2023]

Almammadov T, Dirak M, Saymaz A, Acari A, Kolemen S. A hydrogen sulfide and tyrosinase responsive dual-locked fluorophore for selective imaging of melanoma cells. Chem Commun (Camb) 2023;59:9972-9975. [PMID: 37503543 DOI: 10.1039/d3cc02676k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/29/2023]

Xu H, Li P, Ma H, Tan Y, Wang X, Cai F, Xu J, Sun H, Zhuang H, Hua Z. ADT-OH synergistically enhanced the antitumor activity of celecoxib in human colorectal cancer cells. Cancer Med 2023;12:17193-17211. [PMID: 37492969 PMCID: PMC10501245 DOI: 10.1002/cam4.6342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 06/29/2023] [Accepted: 07/02/2023] [Indexed: 07/27/2023] Open

Ma W, Zhang X, Zhuang L. Exogenous Hydrogen Sulfide Induces A375 Melanoma Cell Apoptosis Through Overactivation of the Unfolded Protein Response. Clin Cosmet Investig Dermatol 2023;16:1641-1651. [PMID: 37396710 PMCID: PMC10314752 DOI: 10.2147/ccid.s412588] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 06/10/2023] [Indexed: 07/04/2023]

Abstract

Purpose

Melanomas are highly malignant and rapidly develop drug resistance due to dysregulated apoptosis. Therefore, pro-apoptotic agents could be effective for the management of melanoma. Hydrogen sulfide is ubiquitous in the body, and exogenous hydrogen sulfide has been reported to show inhibitory and pro-apoptotic effects on cancer cells. However, whether high concentrations of exogenous hydrogen sulfide have pro-apoptotic effects on melanoma and its mechanisms remain unknown. Hence, this study aimed to explore the pro-apoptotic effects and mechanisms of exogenous hydrogen sulfide on the A375 melanoma cell line treated with a hydrogen sulfide donor (NaHS).

Methods

The cell proliferation test, flow cytometric analysis, Hoechst 33258 staining, and Western blotting of B-cell lymphoma 2 and cleaved caspase-3 were used to explore the pro-apoptotic effects of hydrogen sulfide on A375 cells. The transcriptional profile of NaHS-treated A375 cells was further explored via high-throughput sequencing. Western blotting of phosphorylated inositol-requiring enzyme 1α (p-IRE1α), phosphorylated protein kinase R-like ER kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homologous protein, glucose-regulating protein 78, IRE1α, PERK, and eIF2α was performed to verify the changes in the transcriptional profile.

Results

NaHS inhibited A375 melanoma cell proliferation and induced apoptosis. The endoplasmic reticulum stress unfolded protein response and apoptosis-associated gene expression was upregulated in NaHS-treated A375 melanoma cells. The overactivation of the unfolded protein response and increase in endoplasmic reticulum stress was verified at the protein level.

Conclusion

Treatment with NaHS increased endoplasmic reticulum stress, which triggered the overactivation of the unfolded protein response and ultimately lead to melanoma cell apoptosis. The pro-apoptotic effect of NaHS suggests that it can be explored as a potential therapeutic agent in melanoma.

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Xiang J, Wu X, Liu W, Wei H, Zhu Z, Liu S, Song C, Gu Q, Wei S, Zhang Y. Bioinformatic analyzes and validation of cystathionine gamma-lyase as a prognostic biomarker and related to immune infiltrates in hepatocellular carcinoma. Heliyon 2023;9:e16152. [PMID: 37251842 PMCID: PMC10209420 DOI: 10.1016/j.heliyon.2023.e16152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 05/05/2023] [Accepted: 05/07/2023] [Indexed: 05/31/2023] Open

Bello I, Smimmo M, d'Emmanuele di Villa Bianca R, Bucci M, Cirino G, Panza E, Brancaleone V. Erucin, an H₂S-Releasing Isothiocyanate, Exerts Anticancer Effects in Human Triple-Negative Breast Cancer Cells Triggering Autophagy-Dependent Apoptotic Cell Death. Int J Mol Sci 2023;24:ijms24076764. [PMID: 37047736 PMCID: PMC10095418 DOI: 10.3390/ijms24076764] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/29/2023] [Accepted: 04/03/2023] [Indexed: 04/14/2023] Open

Santos SS, Rodrigues LDOCP, Martins V, Petrosino M, Zuhra K, Ascenção K, Anand A, Abdel-Kader RM, Gad MZ, Bourquin C, Szabo C. Role of Cystathionine β-Synthase and 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation, Migration, and Bioenergetics of Murine Breast Cancer Cells. Antioxidants (Basel) 2023;12:antiox12030647. [PMID: 36978895 PMCID: PMC10045476 DOI: 10.3390/antiox12030647] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 02/28/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open

Abstract Cystathionine β-synthase (CBS), CSE (cystathionine γ-lyase) and 3-mercaptopyruvate sulfurtransferase (3-MST) have emerged as three significant sources of hydrogen sulfide (H2S) in various forms of mammalian cancer. Here, we investigated the functional role of CBS’ and 3-MST’s catalytic activity in the murine breast cancer cell line EO771. The CBS/CSE inhibitor aminooxyacetic acid (AOAA) and the 3-MST inhibitor 2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one (HMPSNE) were used to assess the role of endogenous H2S in the modulation of breast cancer cell proliferation, migration, bioenergetics and viability in vitro. Methods included measurements of cell viability (MTT and LDH assays), cell proliferation and in vitro wound healing (IncuCyte) and cellular bioenergetics (Seahorse extracellular flux analysis). CBS and 3-MST, as well as expression were detected by Western blotting; H2S production was measured by the fluorescent dye AzMC. The results show that EO771 cells express CBS, CSE and 3-MST protein, as well as several enzymes involved in H2S degradation (SQR, TST, and ETHE1). Pharmacological inhibition of CBS or 3-MST inhibited H2S production, suppressed cellular bioenergetics and attenuated cell proliferation. Cell migration was only inhibited by the 3-MST inhibitor, but not the CBS/CSE inhibitor. Inhibition of CBS/CSE of 3-MST did not significantly affect basal cell viability; inhibition of 3-MST (but not of CBS/CSE) slightly enhanced the cytotoxic effects of oxidative stress (hydrogen peroxide challenge). From these findings, we conclude that endogenous H2S, generated by 3-MST and to a lower degree by CBS/CSE, significantly contributes to the maintenance of bioenergetics, proliferation and migration in murine breast cancer cells and may also exert a minor role as a cytoprotectant. Collapse

Affiliation(s)

Sidneia Sousa Santos Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina, Federal University of São Paulo (EPM/UNIFESP), São Paulo 04023, Brazil Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Larissa de Oliveira Cavalcanti Peres Rodrigues Department of Medicine, Division of Infectious Diseases, Escola Paulista de Medicina, Federal University of São Paulo (EPM/UNIFESP), São Paulo 04023, Brazil Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Vanessa Martins Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Maria Petrosino Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Karim Zuhra Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Kelly Ascenção Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Abhishek Anand Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
Reham Mahmoud Abdel-Kader Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11511, Egypt
Mohamed Z. Gad Department of Biochemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11511, Egypt
Carole Bourquin School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University of Geneva, 1211 Geneva, Switzerland
Csaba Szabo Chair of Pharmacology, Section of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland Correspondence:

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Rao SP, Dobariya P, Bellamkonda H, More SS. Role of 3-Mercaptopyruvate Sulfurtransferase (3-MST) in Physiology and Disease. Antioxidants (Basel) 2023;12:antiox12030603. [PMID: 36978851 PMCID: PMC10045210 DOI: 10.3390/antiox12030603] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/25/2023] [Accepted: 02/26/2023] [Indexed: 03/05/2023] Open

Rong F, Wang T, Zhou Q, Peng H, Yang J, Fan Q, Li P. Intelligent polymeric hydrogen sulfide delivery systems for therapeutic applications. Bioact Mater 2023;19:198-216. [PMID: 35510171 PMCID: PMC9034248 DOI: 10.1016/j.bioactmat.2022.03.043] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 03/17/2022] [Accepted: 03/29/2022] [Indexed: 12/21/2022] Open

Abstract

Hydrogen sulfide (H₂S) plays an important role in regulating various pathological processes such as protecting mammalian cell from harmful injuries, promoting tissue regeneration, and regulating the process of various diseases caused by physiological disorders. Studies have revealed that the physiological effects of H₂S are highly associated with its concentrations. At relatively low concentration, H₂S shows beneficial functions. However, long-time and high-dose donation of H₂S would inhibit regular biological process, resulting in cell dysfunction and apoptosis. To regulate the dosage of H₂S delivery for precision medicine, H₂S delivery systems with intelligent characteristics were developed and a variety of biocompatibility polymers have been utilized to establish intelligent polymeric H₂S delivery systems, with the abilities to specifically target the lesions, smartly respond to pathological microenvironments, as well as real-timely monitor H₂S delivery and lesion conditions by incorporating imaging-capable moieties. In this review, we focus on the design, preparation, and therapeutic applications of intelligent polymeric H₂S delivery systems in cardiovascular therapy, inflammatory therapy, tissue regenerative therapy, cancer therapy and bacteria-associated therapy. Strategies for precise H₂S therapies especially imaging-guided H₂S theranostics are highlighted. Since H₂S donors with stimuli-responsive characters are vital components for establishing intelligent H₂S delivery systems, the development of H₂S donors is also briefly introduced.

•

H₂S is an endogenous gasotransmitter that plays important role in regulating various physiological and pathological pathways.

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Controlled H₂S delivery is vital since the therapeutic effects of H₂S are highly associated with its concentrations.

•

Intelligent polymeric H₂S delivery systems possess specific targeting, stimuli responsive and imaging guided capabilities, representing a strategic option for next generation of therapies.

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Antiproliferative and Proapoptotic Effects of Erucin, a Diet-Derived H₂S Donor, on Human Melanoma Cells. Antioxidants (Basel) 2022;12:antiox12010041. [PMID: 36670903 PMCID: PMC9854590 DOI: 10.3390/antiox12010041] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 12/19/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022] Open

Zhang Q, Gao Y, Zhang Y, Jing M, Wang D, Wang Y, Khattak S, Qi H, Cai C, Zhang J, Ngowi EE, Khan NH, Li T, Ji A, Jiang Q, Ji X, Li Y, Wu D. Cystathionine γ-lyase mediates cell proliferation, migration, and invasion of nasopharyngeal carcinoma. Oncogene 2022;41:5238-5252. [PMID: 36310322 DOI: 10.1038/s41388-022-02512-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 10/11/2022] [Accepted: 10/13/2022] [Indexed: 12/14/2022]

Affiliation(s)

Qianqian Zhang School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Yingran Gao School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Yanxia Zhang School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Mirong Jing School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Di Wang School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Yizhen Wang School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Saadullah Khattak Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China.,School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China
Huiwen Qi School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Chunbo Cai School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Jing Zhang School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Ebenezeri Erasto Ngowi Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China.,Kaifeng Municipal Key Laboratory of Cell Signal Transduction, Henan Provincial Engineering Centre for Tumor Molecular Medicine, Henan University, Kaifeng, Henan, 475004, China.,Department of Biological Sciences, Faculty of Science, Dar es Salaam University College of Education, Dar es Salaam, 2329, Tanzania
Nazeer Hussain Khan Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China.,School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China
Tao Li School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Ailing Ji School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Qiying Jiang School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China
Xinying Ji School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China. .,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China. .,Kaifeng Municipal Key Laboratory of Cell Signal Transduction, Henan Provincial Engineering Centre for Tumor Molecular Medicine, Henan University, Kaifeng, Henan, 475004, China.
Yanzhang Li School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China. .,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China.
Dongdong Wu School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China. .,Henan International Joint Laboratory for Nuclear Protein Regulation, Henan University, Kaifeng, Henan, 475004, China. .,School of Stomatology, Henan University, Kaifeng, Henan, 475004, China.

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On-demand therapeutic delivery of hydrogen sulfide aided by biomolecules. J Control Release 2022;352:586-599. [PMID: 36328076 DOI: 10.1016/j.jconrel.2022.10.055] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 10/22/2022] [Accepted: 10/26/2022] [Indexed: 11/06/2022]

Ascenção K, Lheimeur B, Szabo C. Regulation of CyR61 expression and release by 3-mercaptopyruvate sulfurtransferase in colon cancer cells. Redox Biol 2022;56:102466. [PMID: 36113340 PMCID: PMC9482125 DOI: 10.1016/j.redox.2022.102466] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 08/29/2022] [Accepted: 09/02/2022] [Indexed: 10/28/2022] Open

Abstract

Cysteine-rich angiogenic inducer 61 (CYR61, also termed CCN family member 1 or CCN1), is a matricellular protein encoded by the CYR61 gene. This protein has been implicated in the regulation of various cancer-associated processes including tumor growth, angiogenesis, tumor cell adhesion, migration, and invasion as well as the regulation of anticancer drug resistance. Hydrogen sulfide (H₂S) is a gaseous endogenous biological mediator, involved in the regulation of cellular bioenergetics, angiogenesis, invasion, and chemotherapeutic resistance in several types of cancer. H₂S is produced by three enzymes: cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST). The current studies were set up to investigate if CBS or 3-MST regulates CyR61 in colon cancer cells in the context of the regulation of proliferation, migration, and survival. The study mainly utilized HCT116 cells, in which two of the principal H₂S-producing enzymes, CBS and 3-MST, are highly expressed. The H₂S donor GYY4137 and the polysulfide donor Na₂S₃ activated the CyR61 promoter in a concentration-dependent fashion. Aminooxyacetic acid (AOAA), a pharmacological inhibitor of CBS as well as HMPSNE: 2-[(4-hydroxy-6- methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one, a pharmacological inhibitor of 3-MST inhibited CyR61 mRNA expression. This effect was more pronounced in response to HMPSNE than to AOAA and occurred through the modulation of S1PR via ATF1 and CREB. CyR61 was found to play an active, but relatively minor role in maintaining colon cell proliferation. HMPSNE markedly suppressed the secretion/release of CyR61 from the colon cancer cells. Moreover, HMPSNE promoted colon cancer cell apoptosis; endogenously produced CyR61 was found to counteract this effect, at least in part via RhoA activation. Taken together, we conclude that the upregulation of 3-MST in cancer cells exerts cytoprotective effects and confers the cancer cells a more aggressive phenotype - at least in part via the modulation of CyR61 expression and release.

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Panza E, Bello I, Smimmo M, Brancaleone V, Mitidieri E, Bucci M, Cirino G, Sorrentino R, D Emmanuele di Villa Bianca R. Endogenous and exogenous hydrogen sulfide modulates urothelial bladder carcinoma development in human cell lines. Biomed Pharmacother 2022;151:113137. [PMID: 35605291 DOI: 10.1016/j.biopha.2022.113137] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/11/2022] [Accepted: 05/15/2022] [Indexed: 11/25/2022] Open

Cai FF, Xu HR, Yu SH, Li P, Lu YY, Chen J, Bi ZQ, Sun HS, Cheng J, Zhuang HQ, Hua ZC. ADT-OH inhibits malignant melanoma metastasis in mice via suppressing CSE/CBS and FAK/Paxillin signaling pathway. Acta Pharmacol Sin 2022;43:1829-1842. [PMID: 34795411 PMCID: PMC9253130 DOI: 10.1038/s41401-021-00799-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Accepted: 10/18/2021] [Indexed: 12/11/2022]

Calvo G, Céspedes M, Casas A, Di Venosa G, Sáenz D. Hydrogen sulfide decreases photodynamic therapy outcome through the modulation of the cellular redox state. Nitric Oxide 2022;125-126:57-68. [PMID: 35728762 DOI: 10.1016/j.niox.2022.06.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 06/06/2022] [Accepted: 06/15/2022] [Indexed: 11/17/2022]

Lohakul J, Jeayeng S, Chaiprasongsuk A, Torregrossa R, Wood ME, Saelim M, Thangboonjit W, Whiteman M, Panich U. Mitochondria-Targeted Hydrogen Sulfide Delivery Molecules Protect Against UVA-Induced Photoaging in Human Dermal Fibroblasts, and in Mouse Skin In Vivo. Antioxid Redox Signal 2022;36:1268-1288. [PMID: 34235951 DOI: 10.1089/ars.2020.8255] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]

Abstract

Aims: Oxidative stress and mitochondrial dysfunction play a role in the process of skin photoaging via activation of matrix metalloproteases (MMPs) and the subsequent degradation of collagen. The activation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor controlling antioxidant and cytoprotective defense systems, might offer a pharmacological approach to prevent skin photoaging. We therefore investigated a pharmacological approach to prevent skin photoaging, and also investigated a protective effect of the novel mitochondria-targeted hydrogen sulfide (H₂S) delivery molecules AP39 and AP123, and nontargeted control molecules, on ultraviolet A light (UVA)-induced photoaging in normal human dermal fibroblasts (NHDFs) in vitro and the skin of BALB/c mice in vivo. Results: In NHDFs, AP39 and AP123 (50-200 nM) but not nontargeted controls suppressed UVA (8 J/cm²)-mediated cytotoxicity and induction of MMP-1 activity, preserved cellular bioenergetics, and increased the expression of collagen and nuclear levels of Nrf2. In in vivo experiments, topical application of AP39 or AP123 (0.3-1 μM/cm²; but not nontargeted control molecules) to mouse skin before UVA (60 J/cm²) irradiation prevented skin thickening, MMP induction, collagen loss of oxidative stress markers 8-hydroxy-2'-deoxyguanosine (8-OHdG), increased Nrf2-dependent signaling, as well as increased manganese superoxide dismutase levels and levels of the mitochondrial biogenesis marker peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α). Innovation and Conclusion: Targeting H₂S delivery to mitochondria may represent a novel approach for the prevention and treatment of skin photoaging, as well as being useful tools for determining the role of mitochondrial H₂S in skin disorders and aging. Antioxid. Redox Signal. 36, 1268-1288.

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Khattak S, Rauf MA, Khan NH, Zhang QQ, Chen HJ, Muhammad P, Ansari MA, Alomary MN, Jahangir M, Zhang CY, Ji XY, Wu DD. Hydrogen Sulfide Biology and Its Role in Cancer. Molecules 2022;27:3389. [PMID: 35684331 PMCID: PMC9181954 DOI: 10.3390/molecules27113389] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/27/2022] [Accepted: 05/01/2022] [Indexed: 02/07/2023] Open

Affiliation(s)

Saadullah Khattak Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China; (S.K.); (N.H.K.); (Q.-Q.Z.); (H.-J.C.)
Mohd Ahmar Rauf Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA;
Nazeer Hussain Khan Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China; (S.K.); (N.H.K.); (Q.-Q.Z.); (H.-J.C.)
Qian-Qian Zhang Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China; (S.K.); (N.H.K.); (Q.-Q.Z.); (H.-J.C.)
Hao-Jie Chen Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China; (S.K.); (N.H.K.); (Q.-Q.Z.); (H.-J.C.)
Pir Muhammad Henan-Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng 475004, China;
Mohammad Azam Ansari Department of Epidemic Disease Research, Institute for Research & Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia;
Mohammad N. Alomary National Centre for Biotechnology, King Abdulaziz City for Science and Technology (KACST), P.O. Box 6086, Riyadh 11442, Saudi Arabia;
Muhammad Jahangir Department of Psychiatric and Mental Health, Central South University, Changsha 410078, China;
Chun-Yang Zhang Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China Department of General Thoracic Surgery, Hami Central Hospital, Hami 839000, China
Xin-Ying Ji Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China; (S.K.); (N.H.K.); (Q.-Q.Z.); (H.-J.C.) Kaifeng Key Laboratory of Infection and Biological Safety, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China
Dong-Dong Wu Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng 475004, China; (S.K.); (N.H.K.); (Q.-Q.Z.); (H.-J.C.) School of Stomatology, Henan University, Kaifeng 475004, China

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Ascenção K, Szabo C. Emerging roles of cystathionine β-synthase in various forms of cancer. Redox Biol 2022;53:102331. [PMID: 35618601 PMCID: PMC9168780 DOI: 10.1016/j.redox.2022.102331] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 04/29/2022] [Accepted: 05/04/2022] [Indexed: 12/12/2022] Open

Cirino G, Szabo C, Papapetropoulos A. Physiological roles of hydrogen sulfide in mammalian cells, tissues and organs. Physiol Rev 2022;103:31-276. [DOI: 10.1152/physrev.00028.2021] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open

Brown EM, Bowden NB. Stabilities of Three Key Biological Trisulfides with Implications for Their Roles in the Release of Hydrogen Sulfide and Bioaccumulation of Sulfane Sulfur. ACS OMEGA 2022;7:11440-11451. [PMID: 35415350 PMCID: PMC8992272 DOI: 10.1021/acsomega.2c00736] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 03/15/2022] [Indexed: 05/28/2023]

Bedi M, Ray M, Ghosh A. Active mitochondrial respiration in cancer: a target for the drug. Mol Cell Biochem 2022;477:345-361. [PMID: 34716860 DOI: 10.1007/s11010-021-04281-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 10/21/2021] [Indexed: 12/21/2022]

Ding H, Chang J, He F, Gai S, Yang P. Hydrogen Sulfide: An Emerging Precision Strategy for Gas Therapy. Adv Healthc Mater 2022;11:e2101984. [PMID: 34788499 DOI: 10.1002/adhm.202101984] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 11/06/2021] [Indexed: 12/13/2022]

Molecular Functions of Hydrogen Sulfide in Cancer. PATHOPHYSIOLOGY 2021;28:437-456. [PMID: 35366284 PMCID: PMC8830448 DOI: 10.3390/pathophysiology28030028] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 09/08/2021] [Accepted: 09/16/2021] [Indexed: 12/30/2022] Open

Nunes SC, Ramos C, Santos I, Mendes C, Silva F, Vicente JB, Pereira SA, Félix A, Gonçalves LG, Serpa J. Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming. Front Cell Dev Biol 2021;9:722412. [PMID: 34458274 PMCID: PMC8386479 DOI: 10.3389/fcell.2021.722412] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 07/13/2021] [Indexed: 01/20/2023] Open

Abstract

Among gynecologic malignancies, ovarian cancer is the third most prevalent and the most common cause of death, especially due to diagnosis at an advanced stage together with resistance to therapy. As a solid tumor grows, cancer cells in the microenvironment are exposed to regions of hypoxia, a selective pressure prompting tumor progression and chemoresistance. We have previously shown that cysteine contributes to the adaptation to this hypoxic microenvironment, but the mechanisms by which cysteine protects ovarian cancer cells from hypoxia-induced death are still to be unveiled. Herein, we hypothesized that cysteine contribution relies on cellular metabolism reprogramming and energy production, being cysteine itself a metabolic source. Our results strongly supported a role of xCT symporter in energy production that requires cysteine metabolism instead of hydrogen sulfide (H2S) per se. Cysteine degradation depends on the action of the H2S-synthesizing enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and/or 3-mercaptopyruvate sulfurtransferase (MpST; together with cysteine aminotransferase, CAT). In normoxia, CBS and CSE inhibition had a mild impact on cysteine-sustained ATP production, pointing out the relevance of CAT + MpST pathway. However, in hypoxia, the concomitant inhibition of CBS and CSE had a stronger impact on ATP synthesis, thus also supporting a role of their hydrogen sulfide and/or cysteine persulfide-synthesizing activity in this stressful condition. However, the relative contributions of each of these enzymes (CBS/CSE/MpST) on cysteine-derived ATP synthesis under hypoxia remains unclear, due to the lack of specific inhibitors. Strikingly, NMR analysis strongly supported a role of cysteine in the whole cellular metabolism rewiring under hypoxia. Additionally, the use of cysteine to supply biosynthesis and bioenergetics was reinforced, bringing cysteine to the plateau of a main carbon sources in cancer. Collectively, this work supports that sulfur and carbon metabolism reprogramming underlies the adaptation to hypoxic microenvironment promoted by cysteine in ovarian cancer.

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Affiliation(s)

Sofia C. Nunes Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Cristiano Ramos Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Inês Santos Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Cindy Mendes Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Fernanda Silva Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
João B. Vicente Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal
Sofia A. Pereira Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal
Ana Félix Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal
Luís G. Gonçalves Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal
Jacinta Serpa Centro de Estudos de Doenças Crónicas, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

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Panieri E, Saso L. Inhibition of the NRF2/KEAP1 Axis: A Promising Therapeutic Strategy to Alter Redox Balance of Cancer Cells. Antioxid Redox Signal 2021;34:1428-1483. [PMID: 33403898 DOI: 10.1089/ars.2020.8146] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]

Abstract

Significance: The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (NRF2/KEAP1) pathway is a crucial and highly conserved defensive system that is required to maintain or restore the intracellular homeostasis in response to oxidative, electrophilic, and other types of stress conditions. The tight control of NRF2 function is maintained by a complex network of biological interactions between positive and negative regulators that ultimately ensure context-specific activation, culminating in the NRF2-driven transcription of cytoprotective genes. Recent Advances: Recent studies indicate that deregulated NRF2 activation is a frequent event in malignant tumors, wherein it is associated with metabolic reprogramming, increased antioxidant capacity, chemoresistance, and poor clinical outcome. On the other hand, the growing interest in the modulation of the cancer cells' redox balance identified NRF2 as an ideal therapeutic target. Critical Issues: For this reason, many efforts have been made to identify potent and selective NRF2 inhibitors that might be used as single agents or adjuvants of anticancer drugs with redox disrupting properties. Despite the lack of specific NRF2 inhibitors still represents a major clinical hurdle, the researchers have exploited alternative strategies to disrupt NRF2 signaling at different levels of its biological activation. Future Directions: Given its dualistic role in tumor initiation and progression, the identification of the appropriate biological context of NRF2 activation and the specific clinicopathological features of patients cohorts wherein its inactivation is expected to have clinical benefits, will represent a major goal in the field of cancer research. In this review, we will briefly describe the structure and function of the NRF2/ KEAP1 system and some of the most promising NRF2 inhibitors, with a particular emphasis on natural compounds and drug repurposing. Antioxid. Redox Signal. 34, 1428-1483.

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Wang RH, Chu YH, Lin KT. The Hidden Role of Hydrogen Sulfide Metabolism in Cancer. Int J Mol Sci 2021;22:ijms22126562. [PMID: 34207284 PMCID: PMC8235762 DOI: 10.3390/ijms22126562] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/24/2021] [Accepted: 06/14/2021] [Indexed: 12/19/2022] Open

Rose P, Moore PK, Whiteman M, Kirk C, Zhu YZ. Diet and Hydrogen Sulfide Production in Mammals. Antioxid Redox Signal 2021;34:1378-1393. [PMID: 33372834 DOI: 10.1089/ars.2020.8217] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]

Abstract

Significance: In recent times, it has emerged that some dietary sulfur compounds can act on mammalian cell signaling systems via their propensity to release hydrogen sulfide (H₂S). H₂S plays important biochemical and physiological roles in the heart, gastrointestinal tract, brain, kidney, and immune systems of mammals. Reduced levels of H₂S in cells and tissues correlate with a spectrum of pathophysiological conditions, including heart disease, diabetes, obesity, and altered immune function. Recent Advances: In the last decade, researchers have now begun to explore the mechanisms by which dietary-derived sulfur compounds, in addition to cysteine, can act as sources of H₂S. This research has led to the identified several compounds, organic sulfides, isothiocyanates, and inorganic sulfur species including sulfate that can act as potential sources of H₂S in mammalian cells and tissues. Critical Issues: We have summarised progress made in the identification of dietary factors that can impact on endogenous H₂S levels in mammals. We also describe current research focused on how some sulfur molecules present in dietary plants, and associated chemical analogues, act as sources of H₂S, and discuss the biological properties of these molecules as studied in a range of in vitro and in vivo systems. Future Directions: The identification of sulfur compounds in edible plants that can act as novel H₂S releasing molecules is intriguing. Research in this area could inform future studies exploring the impact of diet on H₂S levels in mammalian systems. Despite recent progress, additional work is needed to determine the mechanisms by which H₂S is released from these molecules following ingestions of dietary plants in humans, whether the amounts of H₂S produced is of physiological significance following the metabolism of these compounds in vivo, and if diet could be used to manipulated H₂S levels in humans. Importantly, this will lead to a better understanding of the biological significance of H₂S generated from dietary sources, and this information could be used in the development of plant breeding initiatives to increase the levels of H₂S releasing sulfur compounds in crops, or inform dietary intervention strategies that could be used to alter the levels of H₂S in humans.

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The Role of Hydrogen Sulfide in Respiratory Diseases. Biomolecules 2021;11:biom11050682. [PMID: 34062820 PMCID: PMC8147381 DOI: 10.3390/biom11050682] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 04/27/2021] [Accepted: 04/27/2021] [Indexed: 02/08/2023] Open

Hydrogen Sulfide in Skin Diseases: A Novel Mediator and Therapeutic Target. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021;2021:6652086. [PMID: 33986916 PMCID: PMC8079204 DOI: 10.1155/2021/6652086] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 03/25/2021] [Accepted: 04/07/2021] [Indexed: 02/05/2023]

Ascenção K, Dilek N, Augsburger F, Panagaki T, Zuhra K, Szabo C. Pharmacological induction of mesenchymal-epithelial transition via inhibition of H2S biosynthesis and consequent suppression of ACLY activity in colon cancer cells. Pharmacol Res 2021;165:105393. [PMID: 33484818 DOI: 10.1016/j.phrs.2020.105393] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/12/2020] [Accepted: 12/12/2020] [Indexed: 02/07/2023]

Abstract

Hydrogen sulfide (H₂S) is an important endogenous gaseous transmitter mediator, which regulates a variety of cellular functions in autocrine and paracrine manner. The enzymes responsible for the biological generation of H₂S include cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST). Increased expression of these enzymes and overproduction of H₂S has been implicated in essential processes of various cancer cells, including the stimulation of metabolism, maintenance of cell proliferation and cytoprotection. Cancer cell identity is characterized by so-called "transition states". The progression from normal (epithelial) to transformed (mesenchymal) state is termed epithelial-to-mesenchymal transition (EMT) whereby epithelial cells lose their cell-to-cell adhesion capacity and gain mesenchymal characteristics. The transition process can also proceed in the opposite direction, and this process is termed mesenchymal-to-epithelial transition (MET). The current project was designed to determine whether inhibition of endogenous H₂S production in colon cancer cells affects the EMT/MET balance in vitro. Inhibition of H₂S biosynthesis in HCT116 human colon cancer cells was achieved either with aminooxyacetic acid (AOAA) or 2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one (HMPSNE). These inhibitors induced an upregulation of E-cadherin and Zonula occludens-1 (ZO-1) expression and downregulation of fibronectin expression, demonstrating that H₂S biosynthesis inhibitors can produce a pharmacological induction of MET in colon cancer cells. These actions were functionally reflected in an inhibition of cell migration, as demonstrated in an in vitro "scratch wound" assay. The mechanisms involved in the action of endogenously produced H₂S in cancer cells in promoting (or maintaining) EMT (or tonically inhibiting MET) relate, at least in part, in the induction of ATP citrate lyase (ACLY) protein expression, which occurs via upregulation of ACLY mRNA (via activation of the ACLY promoter). ACLY in turn, regulates the Wnt-β-catenin pathway, an essential regulator of the EMT/MET balance. Taken together, pharmacological inhibition of endogenous H₂S biosynthesis in cancer cells induces MET. We hypothesize that this may contribute to anti-cancer / anti-metastatic effects of H₂S biosynthesis inhibitors.

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Xu M, Zhang L, Song S, Pan L, Muhammad Arslan I, Chen Y, Yang S. Hydrogen sulfide: Recent progress and perspectives for the treatment of dermatological diseases. J Adv Res 2020;27:11-17. [PMID: 33318862 PMCID: PMC7728602 DOI: 10.1016/j.jare.2020.02.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 02/07/2020] [Accepted: 02/07/2020] [Indexed: 01/03/2023] Open

Abstract

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Three hydrogen sulfide (H₂S) production enzymes including CSE, CBS and 3-MST exist in the skin.

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H₂S regulates burn, diabetic skin wound, psoriasis, systemic sclerosis, melanoma, and pruritus.

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H₂S regulates oxidative stress, inflammation, angiogenesis and apoptosis in skin diseases.

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Some ideal characteristics of H₂S-based therapeutics for topical delivery are preferred.

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Therapeutic potential of H₂S for skin disorders will be further proposed in clinical trials.

Background

Hydrogen sulfide (H₂S) is now recognized as a vital endogenous gasotransmitter with a variety of biological functions in different systems. Recently, studies have increasingly focused on the role of H₂S in the skin.

Aim of Review

This review summarizes recent progress and provides perspectives on H₂S in the treatment of dermatological diseases.

Key Scientific Concepts of Review

Three H₂S production enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfur transferase (3-MST), are all present in the skin, and it is likely that different cell types in the skin express them differently. Previous studies have demonstrated that H₂S protects against several dermatological diseases, such as burns, diabetic skin wounds, psoriasis, skin flap transplantation, systemic sclerosis, melanoma, and pruritus. The mechanism might be related to the regulation of oxidative stress, inflammation, angiogenesis, apoptosis, and allergic reactions. H₂S-based therapeutics require certain characteristics for topical delivery, for example, controlled release, appropriate physicochemical properties, good storage stability, acceptable odor, and advanced delivery systems. H₂S-induced S-sulfhydration on proteins are potential novel targets for therapeutic intervention and drug design for the skin, which may lead to the development and application of H₂S-related drugs for dermatological diseases.

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Zhang Y, Chen Y, Fang H, Shi X, Yuan H, Bai Y, He W, Guo Z. A ratiometric fluorescent probe for imaging enzyme dependent hydrogen sulfide variation in the mitochondria and in living mice. Analyst 2020;145:5123-5127. [PMID: 32662450 DOI: 10.1039/d0an00910e] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]

Serpa J. Cysteine as a Carbon Source, a Hot Spot in Cancer Cells Survival. Front Oncol 2020;10:947. [PMID: 32714858 PMCID: PMC7344258 DOI: 10.3389/fonc.2020.00947] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 05/14/2020] [Indexed: 12/23/2022] Open