• Apoptosis
• CTCL
• Caspases
• Curcumin
• GADD45
• SKP2

• acetylation
• colon cancer
• curcumin
• epigenetic
• methylation
• methyltransferase
• mutp53
• wtp53

• Humans
• Curcumin/pharmacology
• Colonic Neoplasms/metabolism
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/genetics
• Colonic Neoplasms/pathology
• Lysine/metabolism
• Methylation/drug effects
• HCT116 Cells
• Cell Survival/drug effects
• Apoptosis/drug effects
• Cell Line, Tumor
• Tumor Suppressor Protein p53/genetics
• Tumor Suppressor Protein p53/metabolism
• Histone-Lysine N-Methyltransferase/metabolism
• Histone-Lysine N-Methyltransferase/genetics
• Histone-Lysine N-Methyltransferase/antagonists & inhibitors
• Antineoplastic Agents/pharmacology
• Gene Expression Regulation, Neoplastic/drug effects

• IG2019-23040 Italian Association for Cancer Research

• curcumin
• drug delivery
• laponite
• neutron reflectivity
• supported lipid bilayers

• Curcumin/chemistry
• Curcumin/pharmacology
• Lipid Bilayers/chemistry
• Silicates/chemistry
• Nanoparticles/chemistry
• Drug Delivery Systems/methods
• Humans

• PID2021-129054NA-I00 MICINN
• Materials Physics Center
• DST/INSPIRE/04/2015/001025 India Department of Science
• Provincial Council of Gipuzkoa
• PIBA_2023_1_0054 Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza
• Ikerbasque, Basque Foundation for Science
• MICINN
• Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza
• Ikerbasque, Basque Foundation for Science

• Angiopoietin-like protein 4
• Curcumin
• Fine particulate matter
• Lung inflammation
• PM(2.5)

• Angiopoietin-Like Protein 4/metabolism
• Angiopoietin-Like Protein 4/genetics
• Particulate Matter/toxicity
• Particulate Matter/adverse effects
• Humans
• Pneumonia/chemically induced
• Pneumonia/metabolism
• Pneumonia/pathology
• Pneumonia/prevention & control
• Curcumin/pharmacology
• Lung Neoplasms/chemically induced
• Lung Neoplasms/metabolism
• Lung Neoplasms/pathology
• A549 Cells
• Cytokines/metabolism
• Air Pollutants/toxicity

• Curcumin
• Hematological cancers
• Molecular pathway
• Nanoparticles
• Targeted delivery

• CNC-CTAB
• biological potential
• curcumin
• delivery system
• intestinal permeability

• POCI-01-0247-FEDER-027578 European Regional Development Fund
• UID/Multi/50016/2020 Fundação para a Ciência e Tecnologia

• antifibrotic activity
• chronic liver disease
• hepatic stellate cells
• liver fibrosis
• nanotechnology
• phytoconstituents

• bioinformatics
• cancer
• natural products
• phytochemicals
• synthetic derivatives
• virtual drug screening

• antioxidant
• bioactives
• inflammation
• intestinal permeabilization
• redox

Novel therapeutic strategies are needed in the fight against pancreatic cancer. We have previously documented the chemopreventive effect of MDC-22 in preclinical models of pancreatic cancer. In the present work, we examined the therapeutic effects of MDC-22 in patient-derived tumor xenografts (PDTXs) and in LSL-Kras^G12D/+, LSL-Trp53^R172H/+, Pdx1-Cre (KPC) genetically engineered mice, two complementary and clinically relevant animal models of pancreatic cancer. In addition, we evaluated whether MDC-22 could synergize with current chemotherapeutic drugs used in the clinic. MDC-22 reduced the growth of various human pancreatic cancer cell lines in a concentration-dependent manner. In vivo, MDC-22 strongly reduced patient-derived pancreatic tumor xenograft growth by 50%, and extended survival of LSL-Kras^G12D/+; LSL-Trp53^R172H/+; Pdx1-Cre (KPC) mice by over a month (5.3 months versus 7.0 months). In both models, MDC-22 inhibited EGFR activation and its downstream signals, including ERK and FAK phosphorylation. In human pancreatic cancer cell lines, MDC-22 enhanced the growth inhibitory effect of irinotecan, and to a lesser degree those of gemcitabine and nab-paclitaxel. Normal human pancreatic epithelial cells were more resistant to the cytotoxic effects of, both, MDC-22 alone or in combination with irinotecan, indicating selectivity. Furthermore, MDC-22 enhanced irinotecan's effect on cell migration, in part, by inhibiting EGFR/FAK signaling. Collectively, our results indicate that MDC-22 is an effective anticancer drug in preclinical models of pancreatic cancer, and suggest that MDC-22 plus irinotecan as drug combination strategy for pancreatic cancer treatment, which warrants further evaluation.

• EGFR
• FAK
• KPC
• MDC-22
• Pancreatic cancer
• Phospho-Aspirin
• irinotecan

• Apoptosis
• BAK, Bcl-2 homologous antagonist/killer
• BAX, Bcl-2-Associate X protein
• BCL-XL, B-cell lymphoma-extra large
• Cancer
• HCCLM3
• JAK-1/2, Janus kinase-1/2
• MDA–MB 231
• MMP-2/9, Matrix metalloproteinases-2/9
• MTT, 3-(4, 5-Dimethylthiazol-2-yl) −2,5 diphenyltetrazoliumbromide
• PARP, Poly (ADP-ribose) polymerase
• PIAS-1/3, Protein Inhibitor of Activated STATs-1/3
• Parrotiopsis jacquemontiana
• SHP-1/2, Src-homology region 2 domain-containing phosphatase-1/2
• STAT3
• STAT3, Single transducer and activator of transcription 3
• Stattic
• XIAP, X-linked inhibitor of apoptosis protein

• Epstein-Barr virus
• chemosensitizing
• curcumin
• inorganic arsenic

• 1g
• ER-stress
• ROS—reactive oxygen species
• apoptosis
• colon cancer

• Angiogenesis
• apoptosis
• cancer
• cell cycle
• cell signaling pathways
• clinical trials
• synergistic effect.

• Anti-cancer agents
• Apoptosis
• Bromelain
• Cell-proliferation
• EGCG
• Lymphoma
• MK615
• Natural products
• Resveratrol
• Risk factors

• Antineoplastic Agents, Phytogenic/therapeutic use
• Apoptosis/drug effects
• Cell Cycle/drug effects
• Humans
• Lymphoma/drug therapy
• Lymphoma/metabolism
• Lymphoma/pathology
• Signal Transduction/drug effects

• Cancer related inflammations
• anti-inflammatory
• anticancer activity
• curcumin derivatives
• drug targets
• relationship (SAR)

• Cancer
• Natural compounds
• Polyphenols
• STAT3
• Signaling pathways

• Glioblastoma
• anti-cancer effects
• chemotherapy
• curcumin
• phytochemicals
• temozolomide.

• STAT3
• STAT5
• hematopoietic cancers
• pharmacological inhibitors
• therapeutic targeting

• I 4218 Austrian Science Fund FWF

Acute myeloid leukemia (AML) is a type of blood disorder that exhibits uncontrolled growth and reduced ability to undergo apoptosis. Signal transducer and activator of transcription 3 (STAT3) is a family member of transcription factors which promotes carcinogenesis in most human cancers. This effect on AML is accomplished through deregulation of several critical genes, such as B cell lymphoma-extra-large (BCL-XL) which is anti-apoptotic protein. The aim of this study was to evaluate the effect of curcumin (CUR) and thalidomide (THAL) on apoptosis induction and also the alteration of the mRNA expression level of STAT3 and BCL-XL mRNA on AML cell line compounds.

The growth inhibitory effects of CUR and THAL and their combination were measured by MTT assay in U937 and KG-1 cell lines. The rates of apoptosis induction and cell cycle analysis were measured by concurrent staining with Annexin V and PI. The mRNA expression level of STAT3 and BCL-XL was evaluated by Real-Time PCR.

CUR inhibited proliferation and induced apoptosis in both KG-1 and U937 cells and this effect increased by combination with THAL. The expression level of STAT3 and BCL-XL was significantly down-regulated in KG-1 cells after treatment by CUR and THAL and their combination.

Overall, our findings suggested that down-regulation of STAT3 and BCL-XL mRNA expression in response to CUR and THAL treatment lead to inhibition of cell growth and induction of apoptosis.

• Bcl-xL
• STAT3
• acute myeloid leukemia
• curcumin
• thalidomide

The aim of the present study was to prepare curcumin nanoparticles (nanocurcumin) by a sol-oil method to improve curcumin absorption and bioavailability, and to investigate the therapeutic effects of the prepared nanoparticles on the inhibition mechanisms towards human Hep-2 cancer cells. The nanoparticles were characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction, and zeta potential analysis. The prepared curcumin nanoparticles possessed a narrow particle size distribution with an average diameter of 28 nm. The inhibition effects on the growth of human Hep-2 cells were investigated using neutral red uptake and lactate dehydrogenase assays. The results indicated that the nanocurcumin has a selective effect in inhibiting Hep-2 cell growth in a dose- and time-dependent mode with the most effective IC₅₀ value (17 ± 0.31 μg ml⁻¹) obtained after 48 h of incubation without any cytotoxic effects on normal cells. This IC₅₀ value of nanocurcumin revealed a significant increase of early and late apoptotic cells with an intense comet nucleus of Hep-2 cells as a marker of DNA damage. Flow cytometry analysis of the progression of apoptosis in nanocurcumin Hep-2 treated cells showed that arresting in the cell cycle in the G2/M phase with increasing apoptotic cells in the sub-G1 phase. At the same time, real-time PCR analysis indicated that the treatment of Hep-2 cells with nanocurcumin resulted in upregulation of P53, Bax, and Caspase-3, whereas there was downregulation of Bcl-XL. These findings gave insights into understanding that the inhibition mechanisms of nanocurcumin on the proliferation of Hep-2 cancer cells was through the G2/M cell cycle arrest and the induction of apoptosis was dependent on Caspase-3 and p53 activation. However, in vivo studies with an animal model are essential to validate these results.

The aim of this study was to prepare curcumin nanoparticles using a sol–oil method to improve curcumin absorption and bioavailability, and to investigate the therapeutic effect of the prepared nanoparticles on the inhibition mechanisms toward human Hep-2 cancer cells.

Signal transducer and activator of transcription 3 (STAT3) is an important and the most studied transcription factor in the Janus kinase (JAK)/STAT signaling pathway. STAT3 mediates the expression of various genes that play a critical role in many cellular and biological processes, such as cell proliferation, survival, differentiation, migration, angiogenesis, and inflammation. STAT3 and associated JAKs are activated and tightly regulated by a variety of cytokines and growth factors and their receptors in normal immune responses. However, abnormal expression of STAT3 leads to its constitutive activation, which promotes malignant transformation and tumor progression through oncogenic gene expression in numerous human cancers. Human lymphoma is a heterogeneous malignancy of T and B lymphocytes. Constitutive signaling by STAT3 is an oncogenic driver in several types of B-cell lymphoma and most of T-cell lymphomas. Aberrant STAT3 activation can also induce inappropriate expression of genes involved in tumor immune evasion such as PD-L1. In this review, we focus on the oncogenic role of STAT3 in human lymphoma and highlight potential therapeutic intervention by targeting JAK/STAT3 signaling.

• STAT3
• gene transcription and targeted therapy
• lymphoma
• oncogene

• Akt
• EMT
• epigallocatechin-3-gallate
• gemcitabine
• pancreatic cancer

• Animals
• Antineoplastic Combined Chemotherapy Protocols/pharmacology
• Catechin/analogs & derivatives
• Catechin/pharmacology
• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Deoxycytidine/analogs & derivatives
• Deoxycytidine/pharmacology
• Enzyme Stability
• Epithelial-Mesenchymal Transition/drug effects
• Humans
• Mice, Inbred C57BL
• Neoplasm Invasiveness
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/enzymology
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/pathology
• Proteolysis
• Proto-Oncogene Proteins c-akt/genetics
• Proto-Oncogene Proteins c-akt/metabolism
• Signal Transduction
• Tumor Burden
• Gemcitabine

• Curcumin
• Drug carrier
• Inflammation
• Monocytes
• Pharmaceutical composite
• β-Glucan microparticles

Curcumin (a polyphenolic compound in turmeric) is famous for its potent anti-inflammatory, anti-oxidant, and anti-cancer properties, and has a great potential to act as an epigenetic modulator. The epigenetic regulatory roles of curcumin include the inhibition of DNA methyltransferases (DNMTs), regulation of histone modifications via the regulation of histone acetyltransferases (HATs) and histone deacetylases (HDACs), regulation of microRNAs (miRNA), action as a DNA binding agent and interaction with transcription factors. These mechanisms are interconnected and play a vital role in tumor progression. The recent research has demonstrated the role of epigenetic inactivation of pivotal genes that regulate human pathologies such as cancers. Epigenetics helps to understand the mechanism of chemoprevention of cancer through different therapeutic agents. In this regard, dietary phytochemicals, such as curcumin, have emerged as a potential source to reverse epigenetic modifications and efficiently regulate the expression of genes and molecular targets that are involved in the promotion of tumorigenesis. The curcumin may also act as an epigenetic regulator in neurological disorders, inflammation, and diabetes. Moreover, curcumin can induce the modifications of histones (acetylation/deacetylation), which are among the most important epigenetic changes responsible for altered expression of genes leading to modulating the risks of cancers. Curcumin is an effective medicinal agent, as it regulates several important molecular signaling pathways that modulate survival, govern anti-oxidative properties like nuclear factor E2-related factor 2 (Nrf2) and inflammation pathways, e.g., nuclear factor kappa B (NF-κB). Curcumin is a potent proteasome inhibitor that increases p-53 level and induces apoptosis through caspase activation. Moreover, the disruption of 26S proteasome activity induced by curcumin through inhibiting DYRK2 in different cancerous cells resulting in the inhibition of cell proliferation opens up a new horizon for using curcumin as a potential preventive and treatment approach in proteasome-linked cancers. This review presents a brief summary of knowledge about the mechanism of epigenetic changes induced by curcumin and the potential effects of curcumin such as anti-oxidant activity, enhancement of wound healing, modulation of angiogenesis and its interaction with inflammatory cytokines. The development of curcumin as a clinical molecule for successful chemo-prevention and alternate therapeutic approach needs further mechanistic insights.

• alternative treatment
• angiogenesis
• cancer
• curcumin
• epigenetic modulation

Bovine tropical theileriosis is a tick-borne disease, caused by Theileria annulata which is a protozoan parasite that resides within the B-cells and macrophages. T. annulata is a unique parasite that can transform bovine leucocytes which leads to the cancer hallmarks in the infected cells. Previously, curcumin has been shown to possess multiple pharmacological activities such as anti-inflammatory and anti-cancer activities. In this study, we demonstrated that curcumin inhibits the proliferation of Theileria-transformed bovine leucocytes by promoting apoptosis and autophagy. The transcriptome analysis of curcumin treated cells showed that the genes involved in cell death and autophagy are also differentially regulated. We further elucidated the mechanism of action of curcumin on Theileria infected bovine cells. We found that curcumin induced the generation of reactive oxygen species (ROS) which activated caspase 8 and destabilized the mitochondrial membrane potential leading to the release of cytochrome c from mitochondria. This subsequently led to the activation of caspase 3 and PARP cleavage, finally leading to apoptosis in the infected cells. Furthermore, curcumin induced the process of autophagy which was characterized by the formation of acidic vesicular organelles, LC3B accumulation with lysosome inhibitor, E64d, and the presence of autophagosomes as visualized by transmission electron microscopy (TEM). Curcumin treatment suppressed the mTOR and increased the expression of autophagy-related proteins. We also found that N- acetylcysteine, an inhibitor of ROS, could rescue the infected cells from curcumin induced apoptosis and autophagy mediated cell death. Intriguingly, curcumin had no effect on uninfected bovine PBMCs. Altogether, these data suggest the therapeutic potential of curcumin against bovine tropical theileriosis.

• Antiparasitic agents
• Parasitic infection

• curcuminoid
• microencapsulation
• wound healing

• curcuminoid
• demethoxycurcumin
• enhanced chemical stability
• natural products
• noncancer medical applications

• Anti-cancer herbal medicine
• Anti-cancer natural product
• Biomarker
• Cancer complementary and alternative medicine (CAM)
• Cancer diagnostics
• Integrative oncology

• TLRs
• cancer
• curcumin
• infection
• inflammation
• ischemia

• STAT3
• anti-apoptosis
• hematological malignancies
• proliferation
• targeted inhibition

• cancer
• curcuminoids
• demethoxycurcumin
• metastasis

In the last two decades, targeted therapies have enhanced tumor patient care and treatment success, however, metastatic growth still cannot be stopped efficiently and, therefore, mortality rates remain high. Prevention strategies against formation of metastases are the most promising approach we have, however, due to lack of clinical validation studies, they have not yet entered routine clinical care. In order to smooth the way for efficient prevention, further preclinical and large clinical studies are required. In this context, the underlying molecular mechanisms and factors that lead to metastatic growth have to be explored, and potential preventive agents have to be tested. Thereby, special attention has to be paid to natural bioactive compounds which do not exert major adverse effects, like the plant-derived polyphenol Curcumin, which is known to be a powerful antitumor agent. So far, most of the preclinical studies with Curcumin have focused on its effect on inhibiting tumor cell proliferation and invasion, although, it is known that it also inhibits metastatic spread in vivo. This review discusses the preventive potential of this natural compound not only against tumor onset, but also against formation of metastases.

• cancer
• curcumin
• metastases
• prevention

• CMC2.24
• ERK
• Kras
• Ras
• curcumin
• pancreatic cancer

• Curcumin
• Hodgkin's lymphoma
• SLN
• TPGS

• JNK
• curcumin
• epigenetic regulation
• histone acetylation
• prostate cancer

• Autophagy
• Cancer
• Cell death
• Oxidative stress
• Phytochemical
• Therapy

• AKT/Nrf2
• Apoptosis
• Lung injury
• Luteolin
• Mercury
• NF-κB

The remarkable improvements in the pharmacokinetics and high bioavailability of curcumin polymorphs, amorphous, cocrystals, eutectics, and coamorphous solids are discussed. The importance of pharmaceutical solids in the advanced formulation development of herbal and bioactive molecule curcumin is presented.

Liver fibrosis is a dynamic pathological condition which can be slowed down in its initial phases. Without proper clinical management of fibrosis, progressive liver damage may lead to cirrhosis and ultimately to liver failure or primary liver cancer, which are irreversible conditions. Therefore, in order to cure fibrotic damage to liver, its early stages should be the centre of attention. In this context, some supplements and ‘complementary and alternative medicine (CAM)’ deserve specific mention, because of their already recognized natural way of healing and long lasting curative effects. Moreover, CAM display negligible side effects and hence it is gaining worldwide importance in clinical practices. In particular, herbal medicines are now replacing synthetic pharmaceuticals and looked upon as the sources of novel bioactive substances. To develop satisfactory herbal combinations for treating liver fibrosis, phytoproducts need to be systematically evaluated for their potency as anti-fibrotic, anti-hepatotoxic and antioxidant agents. More importantly, the identified herb/agent should have the remarkable tendency to stimulate hepatocytes regeneration. The present review is a systematic account of at least fifty medicinal herbs and their products which in experimental models have demonstrated antifibrotic activity and thus, most likely candidates to offer therapeutic protection to liver. Nevertheless, much additional work is still needed to explore molecular pathways to discover potential applications of these medicines so as to open up new vistas in biomedical research.

• Complementary and alternative medicine
• Hepatoprotection
• Herbal medicine
• Liver fibrosis
• Phytoproducts

Pancreatic cancer (PC) is one of the most difficult cancers to treat. Since the current chemotherapy is inadequate and various biological approaches have failed, the need for agents that have a potential to treat PC is pressing. Phosphovalproic acid (P-V), a novel anticancer agent, is efficacious in xenograft models of human PC and is apparently safe. In the present study, we evaluated whether formulating P-V in nanoparticles could enhance its anticancer efficacy. In a mouse model of Kras/pancreatitis-associated PC, P-V, orally administered, inhibited the incidence of acinar-to-ductal metaplasia by 60%. To improve its efficacy, we formulated P-V in five different polymeric nanoparticles. Poly-(L)-lactic acid-poly(ethylene glycol) (PLLA-PEG) nanoparticles proved the optimal formulation. PLLA-PEG improved P-V's pharmacokinetics in mice enhancing the levels of P-V in blood. Compared to control, P-V formulated in PLLA-PEG suppressed the growth of MIA PaCa-2 xenografts by 81%, whereas P-V alone reduced it by 51% (P<0.01). Furthermore, P-V formulated in PLLA-PEG inhibited acinar-to-ductal metaplasia in mice with activated Kras, reducing it by 87% (P<0.02). In both disease models, P-V suppressed STAT3 phosphorylation at the Ser727 and Tyr705 residues; STAT3 is the pivotal molecular target of P-V. In conclusion, P-V is a promising agent against PC, and its formulation in PLLA-PEG nanoparticles enhances its efficacy by improving its pharmacokinetics.