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Celik A, Bakar-Ates F. Alpha-lipoic acid induced apoptosis of PC3 prostate cancer cells through an alteration on mitochondrial membrane depolarization and MMP-9 mRNA expression. Med Oncol 2023; 40:244. [PMID: 37453954 DOI: 10.1007/s12032-023-02113-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 07/04/2023] [Indexed: 07/18/2023]
Abstract
Cancer has become an important cause of mortality and morbidity in the world. Over the past decades, biomedical research revealed insights into the molecular events and signaling pathways involved in carcinogenesis and cancer progression. Matrix metalloproteinases (MMPs) are a diverse family of enzymes that can degrade various components of the extracellular matrix and are considered as potential diagnostic and prognostic biomarkers for many cancer types and cancer stages. Recently, studies on the role of natural-origin active substances in the prevention of cancer development gained importance. Among them, the α-lipoic acid, which is commonly found in plants, displayed potent anti-proliferative effects on cancer cell lines. However, the effect of the compound on the induction of apoptosis and mRNA expression of MMPs in human prostate cancer cells remains unclear. The present study aimed to evaluate the anti-proliferative and apoptotic activity of α-lipoic acid in human PC3 prostate carcinoma cells considering different concentrations and exposure durations. The findings showed that, α-lipoic acid significantly decreased PC3 cell viability with an IC50 value of 1.71 mM at 48 h (p < 0.05). Additionally, the compound significantly increased Annexin-V binding in cells compared to control and induced a significant alteration in mitochondrial membrane potential and caspase levels (p < 0.05). Furhermore, the RT-PCR analyses have revealed that α-lipoic acid reduced MMP-9 mRNA expression in PC3 cells compared to the control (p < 0.05). In conclusion, this study highlights that α-lipoic acid induced apoptosis in human PC3 prostate cancer cells and inhibited the MMP-9 gene at the mRNA level, which is known to play a role in metastasis development.
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Affiliation(s)
- Aybuke Celik
- Department of Biochemistry, Faculty of Pharmacy, Ankara University, Anadolu, 06560, Ankara, Turkey
| | - Filiz Bakar-Ates
- Department of Biochemistry, Faculty of Pharmacy, Ankara University, Anadolu, 06560, Ankara, Turkey.
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2
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Bellerba F, Chatziioannou AC, Jasbi P, Robinot N, Keski-Rahkonen P, Trolat A, Vozar B, Hartman SJ, Scalbert A, Bonanni B, Johansson H, Sears DD, Gandini S. Metabolomic profiles of metformin in breast cancer survivors: a pooled analysis of plasmas from two randomized placebo-controlled trials. J Transl Med 2022; 20:629. [PMID: 36581893 PMCID: PMC9798585 DOI: 10.1186/s12967-022-03809-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 12/05/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Obesity is a major health concern for breast cancer survivors, being associated with high recurrence and reduced efficacy during cancer treatment. Metformin treatment is associated with reduced breast cancer incidence, recurrence and mortality. To better understand the underlying mechanisms through which metformin may reduce recurrence, we aimed to conduct metabolic profiling of overweight/obese breast cancer survivors before and after metformin treatment. METHODS Fasting plasma samples from 373 overweight or obese breast cancer survivors randomly assigned to metformin (n = 194) or placebo (n = 179) administration were collected at baseline, after 6 months (Reach For Health trial), and after 12 months (MetBreCS trial). Archival samples were concurrently analyzed using three complementary methods: untargeted LC-QTOF-MS metabolomics, targeted LC-MS metabolomics (AbsoluteIDQ p180, Biocrates), and gas chromatography phospholipid fatty acid assay. Multivariable linear regression models and family-wise error correction were used to identify metabolites that significantly changed after metformin treatment. RESULTS Participants (n = 352) with both baseline and study end point samples available were included in the analysis. After adjusting for confounders such as study center, age, body mass index and false discovery rate, we found that metformin treatment was significantly associated with decreased levels of citrulline, arginine, tyrosine, caffeine, paraxanthine, and theophylline, and increased levels of leucine, isoleucine, proline, 3-methyl-2-oxovalerate, 4-methyl-2-oxovalerate, alanine and indoxyl-sulphate. Long-chain unsaturated phosphatidylcholines (PC ae C36:4, PC ae C38:5, PC ae C36:5 and PC ae C38:6) were significantly decreased with the metformin treatment, as were phospholipid-derived long-chain n-6 fatty acids. The metabolomic profiles of metformin treatment suggest change in specific biochemical pathways known to impair cancer cell growth including activation of CYP1A2, alterations in fatty acid desaturase activity, and altered metabolism of specific amino acids, including impaired branched chain amino acid catabolism. CONCLUSIONS Our results in overweight breast cancer survivors identify new metabolic effects of metformin treatment that may mechanistically contribute to reduced risk of recurrence in this population and reduced obesity-related cancer risk reported in observational studies. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01302379 and EudraCT Protocol #: 2015-001001-14.
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Affiliation(s)
- Federica Bellerba
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | | | - Paniz Jasbi
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
- School of Molecular Sciences, Arizona State University, Tempe, AZ, USA
| | - Nivonirina Robinot
- International Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France
| | - Pekka Keski-Rahkonen
- International Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France
| | - Amarine Trolat
- International Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France
| | - Béatrice Vozar
- International Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France
| | - Sheri J Hartman
- Herbert Wertheim School of Public Health and Human Longevity Science, UC San Diego, La Jolla, CA, USA
- Moores Cancer Center, UC San Diego, La Jolla, CA, USA
| | - Augustin Scalbert
- International Agency for Research on Cancer, Nutrition and Metabolism Branch, Lyon, France
| | - Bernardo Bonanni
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141, Milan, Italy
| | - Harriet Johansson
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Via Giuseppe Ripamonti 435, 20141, Milan, Italy.
| | - Dorothy D Sears
- College of Health Solutions, Arizona State University, Phoenix, AZ, USA
- Moores Cancer Center, UC San Diego, La Jolla, CA, USA
- Department of Medicine, UC San Diego, La Jolla, CA, USA
| | - Sara Gandini
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
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Yuan Q, Xie F, Huang W, Hu M, Yan Q, Chen Z, Zheng Y, Liu L. The review of alpha-linolenic acid: Sources, metabolism, and pharmacology. Phytother Res 2021; 36:164-188. [PMID: 34553434 DOI: 10.1002/ptr.7295] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 08/17/2021] [Accepted: 09/08/2021] [Indexed: 12/18/2022]
Abstract
α-linolenic acid (ALA, 18:3n-3) is a carboxylic acid composed of 18 carbon atoms and three cis double bonds, and is an essential fatty acid indispensable to the human body. This study aims to systematically review related studies on the dietary sources, metabolism, and pharmacological effects of ALA. Information on ALA was collected from the internet database PubMed, Elsevier, ResearchGate, Web of Science, Wiley Online Library, and Europe PMC using a combination of keywords including "pharmacology," "metabolism," "sources." The following findings are mainly contained. (a) ALA can only be ingested from food and then converted into eicosapentaenoic acid and docosahexaenoic acid in the body. (b) This conversion process is relatively limited and affected by many factors such as dose, gender, and disease. (c) Pharmacological research shows that ALA has the anti-metabolic syndrome, anticancer, antiinflammatory, anti-oxidant, anti-obesity, neuroprotection, and regulation of the intestinal flora properties. (d) There are the most studies that prove ALA has anti-metabolic syndrome effects, including experimental studies and clinical trials. (e) The therapeutic effect of ALA will be affected by the dosage. In short, ALA is expected to treat many diseases, but further high quality studies are needed to firmly establish the clinical efficacy of ALA.
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Affiliation(s)
- Qianghua Yuan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Fan Xie
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wei Huang
- Hanyuan Hospital of Traditional Chinese Medicine, Yaan, China
| | - Mei Hu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qilu Yan
- Hanyuan Hospital of Traditional Chinese Medicine, Yaan, China
| | - Zemou Chen
- Hanyuan Hospital of Traditional Chinese Medicine, Yaan, China
| | - Yan Zheng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Li Liu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Buszewska-Forajta M, Raczak-Gutknecht J, Artymowicz M, Wesołowski W, Buczkowski K, Iżycka-Świeszewska E, Markuszewski MJ. The potential role of fatty acids in prostate cancer determined by GC-MS analysis of formalin-fixed paraffin-embedded tissue samples. J Pharm Biomed Anal 2021; 196:113907. [PMID: 33497978 DOI: 10.1016/j.jpba.2021.113907] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 01/11/2021] [Accepted: 01/14/2021] [Indexed: 12/13/2022]
Abstract
Prostate cancer (PCa) is one of the leading types of cancer in men. Although the diagnosis of this disease is currently quite effective, there is still a need to search for noninvasive diagnostic and monitoring methods. Consequently, identifying the mechanisms underlying the development and progression of PCa is crucial. It has been confirmed that the hallmarks of PCa include changes in metabolism, particularly that of fatty acids. Therefore, the application of lipidomics with an accurate histopathological assessment can provide the necessary information and reveal the metabolites that are characteristic of the disease. The use of formalin-fixed, paraffin-embedded (FFPE) tissue samples as an alternative matrix in retrospective research makes this approach highly innovative. The main goal of this study was to perform an untargeted lipidomic analysis of FFPE PCa tissue samples (n = 52) using gas chromatography coupled with mass spectrometry (GC-MS), in comparison to controls (n = 50). To our knowledge, this study is the first to simultaneously conduct a metabolic analysis and histopathological assessment. In the latter, the samples were evaluated based on Gleason grading score and pTNM stage. The obtained results were evaluated by univariate (Student's t-test or Mann-Whitney U-test) as well as multivariate statistical analysis (principal component analysis, partial least squares-discriminant analysis, variable importance into projection, and selectivity ratio) in order to select the metabolites with the most discriminative power. Additionally, the correlation between the level of metabolites and pathological characteristics was determined. The results of the analyses confirmed the changes in the lipid metabolism pathway in PCa. It can be assumed that PCa is linked with elevated de novo biosynthesis of steroid hormone-related fatty acids and beta-oxidation of fatty acids. An increased level of three fatty acids, namely 9-octadecanoic acid, 9,12-octadecadienoic acid, and 5, 8, 1,14-eicosatetraenoic acid, was observed in the PCa samples. These fatty acids were assigned as metabolites with the best discriminative power for the two tested groups. In practice, these compounds could be considered as specific biochemical factors that may be implemented in the diagnosis of PCa, but their significance should be validated on a more extensive set of samples. Undoubtedly, these results are valuable as they provide important information on prostate cancerogenesis in the context of a metabolic switch.
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Affiliation(s)
- Magdalena Buszewska-Forajta
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland.
| | - Joanna Raczak-Gutknecht
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland
| | - Małgorzata Artymowicz
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland
| | - Wojciech Wesołowski
- Department of Pathology and Neuropathology, Medical University of Gdańsk, Dębinki 1, 80-211, Gdańsk, Poland; ELPAT Department of Pathomorphology, Królewiecka 146, 82-300, Elbląg, Poland
| | - Kamil Buczkowski
- Department of Pathomorphology, Copernicus Hospitals, Nowe Ogrody 1-6, 80-803, Gdańsk, Poland
| | - Ewa Iżycka-Świeszewska
- Department of Pathology and Neuropathology, Medical University of Gdańsk, Dębinki 1, 80-211, Gdańsk, Poland; Department of Pathomorphology, Copernicus Hospitals, Nowe Ogrody 1-6, 80-803, Gdańsk, Poland
| | - Michał J Markuszewski
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416, Gdańsk, Poland
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Feng LM, Chen YY, Xu DQ, Fu RJ, Yue SJ, Zhao Q, Huang YX, Bai X, Wang M, Xing LM, Tang YP, Duan JA. An integrated strategy for discovering effective components of Shaoyao Gancao decoction for treating neuropathic pain by the combination of partial least-squares regression and multi-index comprehensive method. JOURNAL OF ETHNOPHARMACOLOGY 2020; 260:113050. [PMID: 32502651 DOI: 10.1016/j.jep.2020.113050] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 05/14/2020] [Accepted: 05/30/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Neuropathic pain, the incidence of which ranges from 5 to 8% in the general population, remains challenge in the treatment. Shaoyao Gancao decoction (SGD) is a Chinese classical formula used to relieve pain for thousands of years and has been applied for neuropathic pain nowadays. However, the effective components of SGD for the treatment of neuropathic pain remains unclear. AIMS OF STUDY To investigate the effect and potential mechanism of SGD against neuropathic pain and further reveal the effective components of SGD in the treatment of neuropathic pain. MATERIALS AND METHODS Spared nerve injury (SNI) model rats of neuropathic pain were orally given SGD to intervene, the components in vivo after SGD administration were determined, behavior indicators, biochemical parameters, and metabolomics were applied for assessing the efficacy. Then correlation between components and biomarkers was analyzed by pearson correlation method. To further measure the contribution of components to efficacy, the combination of partial least-squares regression (PLSR) and multi-index comprehensive method was carried out, according to the corresponding contribution degree of the results, the components with large contribution degree were considered as the effective components. RESULTS SGD exhibited a significant regulatory effect on neuropathic pain, which could increase the pain threshold and decrease the levels of SP, β-EP, PGE2 and NO. With the high resolution of UPLC-Q-TOF/MS technology, a total of 128 compounds from SGD were identified and 44 of them were absorbed in blood. Besides, 40 serum biomarkers were identified after intervention of SGD and the metabolic pathways were constructed. The key metabolic pathways including Glycerophospholipid metabolism, Linoleic acid metabolism, Alpha-linolenic acid metabolism, Glycosylphosphatidylinositol-anchor biosynthesis and Arachidonic acid metabolism may be related to the regulation of neuropathic pain. Metabolomics combined with PLSR and multi-index comprehensive method was utilized to discover 5 components including paeonol, DL-Arabinose, benzoic acid, hispaglabridin A and paeonilactone C as effective components of SGD in the treatment of neuropathic pain. This strategy was used to explore the effective components of SGD and elucidate its possible analgesic mechanism. CONCLUSION This study demonstrate that SGD significantly relieved neuropathic pain and elucidated the effective components of SGD for treating neuropathic pain, the strategy as an illustrative case study can be applied to other classical formula and is beneficial to improve the quality and efficacy.
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Affiliation(s)
- Li-Mei Feng
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Yan-Yan Chen
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China.
| | - Ding-Qiao Xu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Rui-Jia Fu
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Shi-Jun Yue
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Qi Zhao
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Yu-Xi Huang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Xue Bai
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Mei Wang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Li-Ming Xing
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China
| | - Yu-Ping Tang
- Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, 712046, Shaanxi Province, China.
| | - Jin-Ao Duan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu Province, China
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Huang Y, Chang A, Zhou W, Zhao H, Zhuo X. IGFBP3 as an indicator of lymph node metastasis and unfavorable prognosis for papillary thyroid carcinoma. Clin Exp Med 2020; 20:515-525. [PMID: 32596748 DOI: 10.1007/s10238-020-00642-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 06/17/2020] [Indexed: 12/01/2022]
Abstract
Lymph node metastasis (LNM) is a usual event in papillary thyroid carcinoma (PTC) patients, which usually leads to poor prognosis. However, the molecular mechanisms of LNM remain unclear. Thus, we aimed to screen the possible key genes in the progression of LNM in PTC patients and further validate their roles. The study involved two phases: a discovery phase and a validation one. In the former phase, the candidate genes were screened by using bioinformatics methods. In the latter one, the genes were firstly assessed in a cohort from the cancer genome atlas (TCGA) to evaluate the associations of their expressions with clinical features and the prognostic values, and then, they were assessed at protein levels by using an immunohistochemical assay. Consequently, IGHBP3 was selected as the candidate gene, which might be enriched in several metabolism-related pathways and cancer progression-related pathways. High expressions of IGHBP3 have an association with gender, advanced clinical stages, high T stages, and the presence of LNM. Survival analysis indicated that IGHBP3 may affect the prognosis of PTC patients. The use of a tissue chip confirmed the view that IGHBP3 might play a crucial role in the LNM of PTC. In conclusion, IGHBP3 might be involved in the development of LNM in PTC patients. IGHBP3 over-expression might be a novel indicator and a potential target for PTC therapy.
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Affiliation(s)
- Yi Huang
- Affiliated Hospital of Guiyang Medical University, Guiyang, China
| | - Aoshuang Chang
- Affiliated Hospital of Guiyang Medical University, Guiyang, China
| | - Wei Zhou
- Chongqing Cancer Institute, Chongqing, China
| | - Houyu Zhao
- Affiliated Hospital of Guiyang Medical University, Guiyang, China
| | - Xianlu Zhuo
- Affiliated Hospital of Guiyang Medical University, Guiyang, China.
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Li P, Shan B, Jia K, Hu F, Xiao Y, Zheng J, Gao YT, Wang H, Gao Y. Plasma omega-3 polyunsaturated fatty acids and recurrence of endometrial cancer. BMC Cancer 2020; 20:576. [PMID: 32563240 PMCID: PMC7305622 DOI: 10.1186/s12885-020-07035-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 06/03/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Omega-3 polyunsaturated fatty acids (PUFAs) were proposed to have potential effects against inflammation and cancer. However, results from epidemiology studies remain inconsistent. We aimed to explore the associations of plasma PUFAs with EC recurrence and all-cause mortality. METHOD Women diagnosed with endometrial cancer (EC) between 2008 and 2013 and underwent surgery at Fudan University Shanghai Cancer Center of China were recruited. Survival status was followed up through September 2017. EC recurrence and total cause deaths were identified through medical record and telephone interview. In total, 202 patients with enough plasma samples at time of surgery were included. There were 195 patients who provided baseline plasma and survival information included in the current study. Plasma omega-3 PUFAs were measured by GC-FID. Cox Proportional Hazard model adjusted for potential cofounders was used to estimate HRs and 95% CIs. RESULTS Median follow-up time for patients was 58 months after surgery. A total of 13 recurrences and 11 all-cause deaths, of which, 2 deaths from EC, were identified. Level of plasma EPA was higher in recurrent patients than total patients (0.78% vs 0.51%, P = 0.015). Higher plasma eicosapentaenoic acid (EPA) level trended to have positive association with EC recurrence (P-trend = 0.04), although comparing to the lowest tertile, the highest tertile of EPA level was not significantly associated with increased risk of EC recurrence (HRT3vsT1 = 6.02; 95%CI = 0.7-52.06). The association between total omega-3 PUFA and EC recurrence tended to be stronger among patients with deeper myometrial invasion (OR = 3.41; 95%CI = 1.06-10.95; P-interaction = 0.04). CONCLUSIONS Higher plasma EPA level was significantly associated with EC recurrence. Further studies are warranted to confirm these findings. TRIAL REGISTRATION ChiCTR1900025418; Retrospectively registered (26 August 2019); Chinses Clinical Trial Registry.
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Affiliation(s)
- Peiqin Li
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
| | - Boer Shan
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Keyu Jia
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
| | - Fan Hu
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China
| | - Ying Xiao
- Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China
| | - Jusheng Zheng
- School of Life Sciences, Westlake University, Hangzhou, China
| | - Yu-Tang Gao
- Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China
| | - Huaying Wang
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Ying Gao
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
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Du WB, Lin CH, Chen WB. High expression of APC is an unfavorable prognostic biomarker in T4 gastric cancer patients. World J Gastroenterol 2019; 25:4452-4467. [PMID: 31496624 PMCID: PMC6710185 DOI: 10.3748/wjg.v25.i31.4452] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 07/18/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Adenoma polyposis coli (APC) mutation is associated with tumorigenesis via the Wnt signaling pathway. AIM To investigate the clinical features and mechanism of APC expression in gastric cancer (GC). METHODS Based on APC expression profile, the related genome-wide mRNA expression, microRNA (miRNA) expression, and methylation profile in GC, the relationship between APC and GC, as well as the prognostic significance of APC were systematically analyzed by multi-dimensional methods. RESULTS We found that high expression of APC (APC high) was significantly associated with adverse outcomes of T4 GC patients. Genome-wide gene expression analysis revealed that varying APC expression levels in GC were associated with some important oncogenes, and corresponding cellular functional pathways. Genome-wide miRNA expression analysis indicated that most of miRNAs associated with high APC expression were downregulated. The mRNA-miRNA regulatory network analysis revealed that down-regulated miRNAs affected their inhibitory effect on tumor genes. Genome-wide methylation profiles associated with APC expression showed that there was differential methylation between the APC high and APC low groups. The number of hypermethylation sites was larger than that of hypomethylation sites, and most of hypermethylation sites were enriched in CpG islands. CONCLUSION Our research demonstrated that high APC expression is an unfavorable prognostic factor for T4 GC patients and may be used as a novel biomarker for pathogenesis research, diagnosis, and treatment of GC.
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Affiliation(s)
- Wei-Bo Du
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Chen-Hong Lin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
| | - Wen-Biao Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
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Yoo JK, Lee JM, Kang SH, Jeon SH, Kim CM, Oh SH, Kim CH, Kim NK, Kim JK. The novel microRNA hsa-miR-CHA1 regulates cell proliferation and apoptosis in human lung cancer by targeting XIAP. Lung Cancer 2019; 132:99-106. [DOI: 10.1016/j.lungcan.2018.04.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Revised: 04/04/2018] [Accepted: 04/12/2018] [Indexed: 12/29/2022]
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Liyanage UE, Ong JS, An J, Gharahkhani P, Law MH, MacGregor S. Mendelian Randomization Study for Genetically Predicted Polyunsaturated Fatty Acids Levels on Overall Cancer Risk and Mortality. Cancer Epidemiol Biomarkers Prev 2019; 28:1015-1023. [DOI: 10.1158/1055-9965.epi-18-0940] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 12/06/2018] [Accepted: 03/27/2019] [Indexed: 11/16/2022] Open
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11
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Abstract
For decades, dietary advice was based on the premise that high intakes of fat cause obesity, diabetes, heart disease, and possibly cancer. Recently, evidence for the adverse metabolic effects of processed carbohydrate has led to a resurgence in interest in lower-carbohydrate and ketogenic diets with high fat content. However, some argue that the relative quantity of dietary fat and carbohydrate has little relevance to health and that focus should instead be placed on which particular fat or carbohydrate sources are consumed. This review, by nutrition scientists with widely varying perspectives, summarizes existing evidence to identify areas of broad consensus amid ongoing controversy regarding macronutrients and chronic disease.
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Affiliation(s)
- David S Ludwig
- New Balance Foundation Obesity Prevention Center, Boston Children's Hospital, Boston, MA, USA. .,Harvard Medical School, Boston, MA, USA
| | - Walter C Willett
- Harvard Medical School, Boston, MA, USA.,Departments of Epidemiology and Nutrition, Harvard T. H. Chan School of Public Health and Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Jeff S Volek
- Department of Human Sciences, The Ohio State University, Columbus, OH, USA
| | - Marian L Neuhouser
- Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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12
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McCarty MF, DiNicolantonio JJ. Minimizing Membrane Arachidonic Acid Content as a Strategy for Controlling Cancer: A Review. Nutr Cancer 2018; 70:840-850. [DOI: 10.1080/01635581.2018.1470657] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
| | - James J. DiNicolantonio
- Preventive Cardiology Department, St. Luke’s Mid America Heart Institute, Kansas City, Missouri, USA
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13
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Cacciatore S, Zadra G, Bango C, Penney KL, Tyekucheva S, Yanes O, Loda M. Metabolic Profiling in Formalin-Fixed and Paraffin-Embedded Prostate Cancer Tissues. Mol Cancer Res 2017; 15:439-447. [PMID: 28074002 DOI: 10.1158/1541-7786.mcr-16-0262] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Revised: 12/09/2016] [Accepted: 12/22/2016] [Indexed: 12/28/2022]
Abstract
Metabolite profiling has significantly contributed to a deeper understanding of the biochemical metabolic networks and pathways in cancer cells. Metabolomics-based biomarker discovery would greatly benefit from the ability to interrogate retrospective annotated clinical specimens archived as formalin-fixed, paraffin-embedded (FFPE) material. Mass spectrometry-based metabolomic analysis was performed in matched frozen and FFPE human prostate cancers as well as isogenic prostate cancer cell lines. A total of 352 and 460 metabolites were profiled in human tissues and cell lines, respectively. Classes and physical-chemical characteristics of the metabolites preserved in FFPE material were characterized and related to their preservation or loss following fixation and embedding. Metabolite classes were differentially preserved in archival FFPE tissues, regardless of the age of the block, compared with matched frozen specimen, ranging from maximal preservation of fatty acids (78%) to loss of the majority of peptides and steroids. Generally, FFPE samples showed a decrease of metabolites with functional groups, such as carboxamide. As an adjunct technique, metabolic profiles were also obtained in situ from FFPE tissue sections where metabolites were extracted in a manner that preserves tissue architecture. Despite the fact that selected metabolites were not retained after processing, global metabolic profiles obtained from FFPE can be used to predict biologic states and study biologic pathways. These results pave the way for metabolomics-based biomarker discovery/validation utilizing retrospective and clinically annotated FFPE collections.Implications: Metabolic profiles can be performed in archival tissue and may be used to complement other profiling methods such as gene expression for biomarker discovery or pathway analysis in the assessment of biologic states. Mol Cancer Res; 15(4); 439-47. ©2017 AACR.
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Affiliation(s)
- Stefano Cacciatore
- Department of Medical Oncology, Center of Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.,Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom
| | - Giorgia Zadra
- Department of Medical Oncology, Center of Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.,Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Clyde Bango
- Department of Medical Oncology, Center of Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
| | - Kathryn L Penney
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Svitlana Tyekucheva
- Departments of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.,Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Oscar Yanes
- Centre for Omic Sciences, Rovira i Virgili University, Reus, Spain.,Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
| | - Massimo Loda
- Department of Medical Oncology, Center of Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. .,Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.,The Broad Institute, Cambridge, Boston, Massachusetts.,Division of Cancer Studies, King's College London, London, United Kingdom
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14
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Duscharla D, Bhumireddy SR, Lakshetti S, Pospisil H, Murthy PVLN, Walther R, Sripadi P, Ummanni R. Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers. PLoS One 2016; 11:e0150253. [PMID: 26958841 PMCID: PMC4784901 DOI: 10.1371/journal.pone.0150253] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Accepted: 02/11/2016] [Indexed: 12/14/2022] Open
Abstract
Prostate cancer (PCa) is one amongst the most common cancersin western men. Incidence rate ofPCa is on the rise worldwide. The present study deals with theserum lipidome profiling of patients diagnosed with PCa to identify potential new biomarkers. We employed ESI-MS/MS and GC-MS for identification of significantly altered lipids in cancer patient’s serum compared to controls. Lipidomic data revealed 24 lipids are significantly altered in cancer patinet’s serum (n = 18) compared to normal (n = 18) with no history of PCa. By using hierarchical clustering and principal component analysis (PCA) we could clearly separate cancer patients from control group. Correlation and partition analysis along with Formal Concept Analysis (FCA) have identified that PC (39:6) and FA (22:3) could classify samples with higher certainty. Both the lipids, PC (39:6) and FA (22:3) could influence the cataloging of patients with 100% sensitivity (all 18 control samples are classified correctly) and 77.7% specificity (of 18 tumor samples 4 samples are misclassified) with p-value of 1.612×10−6 in Fischer’s exact test. Further, we performed GC-MS to denote fatty acids altered in PCa patients and found that alpha-linolenic acid (ALA) levels are altered in PCa. We also performed an in vitro proliferation assay to determine the effect of ALA in survival of classical human PCa cell lines LNCaP and PC3. We hereby report that the altered lipids PC (39:6) and FA (22:3) offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis.
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Affiliation(s)
- Divya Duscharla
- Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
- Centre for Academy of Scientific & Innovative Research, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
| | - Sudarshana Reddy Bhumireddy
- Centre for Academy of Scientific & Innovative Research, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
- National Centre for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
| | - Sridhar Lakshetti
- National Centre for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
| | - Heike Pospisil
- High Performance Computing in Life Sciences, Technical University, Wildau, Germany
| | - P. V. L. N. Murthy
- Department of Urology, Nizam’s Institute of Medical Sciences (NIMS), Hyderabad, India
| | - Reinhard Walther
- Department of Medical Biochemistry and Molecular Biology, University of Greifswald, Greifswald, Germany
| | - Prabhakar Sripadi
- Centre for Academy of Scientific & Innovative Research, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
- National Centre for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
| | - Ramesh Ummanni
- Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
- Centre for Academy of Scientific & Innovative Research, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, India
- * E-mail:
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15
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Cancer Risk and Eicosanoid Production: Interaction between the Protective Effect of Long Chain Omega-3 Polyunsaturated Fatty Acid Intake and Genotype. J Clin Med 2016; 5:jcm5020025. [PMID: 26891335 PMCID: PMC4773781 DOI: 10.3390/jcm5020025] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2015] [Revised: 01/15/2016] [Accepted: 02/02/2016] [Indexed: 01/11/2023] Open
Abstract
Dietary inclusion of fish and fish supplements as a means to improve cancer prognosis and prevent tumour growth is largely controversial. Long chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA), eicosapentaenoic acid and docosahexaenoic acid, may modulate the production of inflammatory eicosanoids, thereby influencing local inflammatory status, which is important in cancer development. Although in vitro studies have demonstrated inhibition of tumour cell growth and proliferation by LCn-3 PUFA, results from human studies have been mainly inconsistent. Genes involved in the desaturation of fatty acids, as well as the genes encoding enzymes responsible for eicosanoid production, are known to be implicated in tumour development. This review discusses the current evidence for an interaction between genetic polymorphisms and dietary LCn-3 PUFA in the risk for breast, prostate and colorectal cancers, in regards to inflammation and eicosanoid synthesis.
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16
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Fu YQ, Zheng JS, Yang B, Li D. Effect of individual omega-3 fatty acids on the risk of prostate cancer: a systematic review and dose-response meta-analysis of prospective cohort studies. J Epidemiol 2015; 25:261-74. [PMID: 25787237 PMCID: PMC4375280 DOI: 10.2188/jea.je20140120] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Epidemiological studies have suggested inconsistent associations between omega-3 polyunsaturated fatty acids (n-3 PUFAs) and prostate cancer (PCa) risk. We performed a dose-response meta-analysis of prospective observational studies investigating both dietary intake and circulating n-3 PUFAs and PCa risk. PubMed and EMBASE prior to February 2014 were searched, and 16 publications were eligible. Blood concentration of docosahexaenoic acid, but not alpha-linolenic acid or eicosapentaenoic acid, showed marginal positive association with PCa risk (relative risk for 1% increase in blood docosahexaenoic acid concentration: 1.02; 95% confidence interval, 1.00-1.05; I(2) = 26%; P = 0.05 for linear trend), while dietary docosahexaenoic acid intake showed a non-linear positive association with PCa risk (P < 0.01). Dietary alpha-linolenic acid was inversely associated with PCa risk (relative risk for 0.5 g/day increase in alpha-linolenic acid intake: 0.99; 95% confidence interval, 0.98-1.00; I(2) = 0%; P = 0.04 for linear trend), which was dominated by a single study. Subgroup analyses indicated that blood eicosapentaenoic acid concentration and blood docosahexaenoic acid concentration were positively associated with aggressive PCa risk and nonaggressive PCa risk, respectively. Among studies with nested case-control study designs, a 0.2% increase in blood docosapentaenoic acid concentration was associated with a 3% reduced risk of PCa (relative risk 0.97; 95% confidence interval, 0.94-1.00; I(2) = 44%; P = 0.05 for linear trend). In conclusion, different individual n-3 PUFA exposures may exhibit different or even opposite associations with PCa risk, and more prospective studies, especially those examining dietary n-3 PUFAs and PCa risk stratified by severity of cancer, are needed to confirm the results.
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Affiliation(s)
- Yuan-Qing Fu
- Department of Food Science and Nutrition, Zhejiang University
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17
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Mandair D, Rossi RE, Pericleous M, Whyand T, Caplin ME. Prostate cancer and the influence of dietary factors and supplements: a systematic review. Nutr Metab (Lond) 2014; 11:30. [PMID: 24976856 PMCID: PMC4073189 DOI: 10.1186/1743-7075-11-30] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2014] [Accepted: 05/24/2014] [Indexed: 12/20/2022] Open
Abstract
Background Prostate cancer is the second most common cause of cancer worldwide after lung cancer. There is increasing evidence that diet and lifestyle plays a crucial role in prostate cancer biology and tumourigenesis. Prostate cancer itself represents a good model of cancer in which to look for chemopreventive agents due to the high disease prevalence, slowly progressive nature, and long latency period. Dietary agents have gained considerable attention, often receiving much publicity in the media. Aim To review the key evidence available for potential chemopreventive nutrients. Methods The methodology for this review involved a PubMed search from 1990 to 2013 using the key-words “diet and prostate cancer”, “nutrition and prostate cancer”, “dietary factors and prostate cancer”, “prostate cancer epidemiology”, “prostate cancer prevention”, “prostate cancer progression”. Results Red meat, dietary fat and milk intake should be minimised as they appear to increase the risk of prostate cancer. Fruit and vegetables and polyphenols may be preventive in prostate cancer, but further studies are needed to draw more solid conclusions and to clarify their role in patients with an established diagnosis of prostate cancer. Selenium and vitamin supplements cannot be advocated for the prevention of prostate cancer and indeed higher doses may be associated with a worse prognosis. There is no specific evidence regarding benefits of probiotics or prebiotics in prostate cancer. Conclusions From the wealth of evidence available, many recommendations can be made although more randomised control trials are required. These need to be carefully designed due to the many confounding factors and heterogeneity of the population.
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Affiliation(s)
- Dalvinder Mandair
- Centre for Gastroenterology, Royal Free Hospital, Pond Street, London NW3 2QG, UK ; Cancer Institute, University College London, Huntley Street, London, UK
| | - Roberta Elisa Rossi
- Centre for Gastroenterology, Royal Free Hospital, Pond Street, London NW3 2QG, UK ; Department of Pathophysiology and Organ Transplant, Universita' degli Studi di Milano and Gastroenterology Unit II, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Marinos Pericleous
- Centre for Gastroenterology, Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - Tara Whyand
- Department of Nutrition and Dietetics, Royal Free Hospital, London, UK
| | - Martyn Evan Caplin
- Centre for Gastroenterology, Royal Free Hospital, Pond Street, London NW3 2QG, UK
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18
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Azrad M, Turgeon C, Demark-Wahnefried W. Current evidence linking polyunsaturated Fatty acids with cancer risk and progression. Front Oncol 2013; 3:224. [PMID: 24027672 PMCID: PMC3761560 DOI: 10.3389/fonc.2013.00224] [Citation(s) in RCA: 111] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Accepted: 08/15/2013] [Indexed: 12/14/2022] Open
Abstract
There is increasing evidence that polyunsaturated fatty acids (PUFAs) play a role in cancer risk and progression. The n-3 family of PUFAs includes alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) while the n-6 family includes linolenic acid (LA) and arachidonic acid (AA). EPA and DHA are precursors for anti-inflammatory lipid mediators while AA is a precursor for pro-inflammatory lipid mediators. Collectively, PUFAs play crucial roles in maintaining cellular homeostasis, and perturbations in dietary intake or PUFA metabolism could result in cellular dysfunction and contribute to cancer risk and progression. Epidemiologic studies provide an inconsistent picture of the associations between dietary PUFAs and cancer. This discrepancy may reflect the difficulties in collecting accurate dietary data; however, it also may reflect genetic variation in PUFA metabolism which has been shown to modify physiological levels of PUFAs and cancer risk. Also, host-specific mutations as a result of cellular transformation could modify metabolism of PUFAs in the target-tissue. Clinical trials have shown that supplementation with PUFAs or foods high in PUFAs can affect markers of inflammation, immune function, tumor biology, and prognosis. Pre-clinical investigations have begun to elucidate how PUFAs may mediate cell proliferation, apoptosis and angiogenesis, and the signaling pathways involved in these processes. The purpose of this review is to summarize the current evidence linking PUFAs and their metabolites with cancer and the molecular mechanisms that underlie this association. Identifying the molecular mechanism(s) through which PUFAs affect cancer risk and progression will provide an opportunity to pursue focused dietary interventions that could translate into the development of personalized diets for cancer control.
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Affiliation(s)
- Maria Azrad
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Chelsea Turgeon
- School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Wendy Demark-Wahnefried
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
- Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
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