Association of p38MAPK‐p53‐Fas aggregation in S‐allyl cysteine mediated regulation of hepatocarcinoma
| Autor: | Kaustav Dutta Chowdhury, Gobinda Chandra Sadhukhan, Sujan Chatterjee, Udipta Chakraborti, Pujita Ghosh, Anupam Basu, Dipanwita Sengupta, Debajyoti Patra |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Fas Ligand Protein Pyridines Health Toxicology and Mutagenesis p38 mitogen-activated protein kinases Cell S-Allyl cysteine Antineoplastic Agents 010501 environmental sciences Management Monitoring Policy and Law Toxicology p38 Mitogen-Activated Protein Kinases 01 natural sciences Mice 03 medical and health sciences chemistry.chemical_compound Liver Neoplasms Experimental 0302 clinical medicine medicine Animals Humans Cysteine fas Receptor Phosphorylation Protein Kinase Inhibitors Caspase 0105 earth and related environmental sciences biology Chemistry Cell growth Imidazoles Hep G2 Cells General Medicine medicine.anatomical_structure Apoptosis Caspases 030220 oncology & carcinogenesis Death-inducing signaling complex biology.protein Cancer research Tumor Suppressor Protein p53 |
| Zdroj: | Environmental Toxicology. 34:928-940 |
| ISSN: | 1522-7278 1520-4081 |
| DOI: | 10.1002/tox.22764 |
| Popis: | Bioactive components of dietary phytochemicals have been reported to possess antitumor activities. Evidences suggested key role of stress responsive p38MAPK in the induction of nutraceuticals mediated apoptosis in hepatocellular carcinoma (HCC). Current study demonstrated detailed molecular bagatelle associated with p38 MAPK mediated effective suppression of cell growth both in HepG2 and chemically induced liver carcinoma after S-allyl cysteine (SAC) treatment. SAC promoted p38MAPK activity responsible for p53 phosphorylation, its stabilization followed by nuclear translocation leading to induction in expression and oligomerization of Fas protein. Distinctive p38MAPK-p53 axis dependent Fas-FasL-FADD mediated caspase activities along with perturbed cell cycling became normalized with continuation of SAC treatment for another month to diethylnitrosamine induced liver carcinoma. Co-treatment with SB203580, the p38MAPK inhibitor, prevented pro-apoptotic effect of SAC by altering p53 phosphorylation and death inducing signaling complex conformation in HepG2 and induced HCC. Collectively study suggested significant contribution of p38MAPK-p53-DISC-Caspase pathway in the regulation of anti-neoplastic activity of SAC against HCC. |
| Databáze: | OpenAIRE |
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