AI Article Synopsis

  • Bioactive compounds in dietary phytochemicals, like S-allyl cysteine (SAC), have been found to have anti-tumor properties, particularly in liver cancer.
  • The study highlights the role of the stress-responsive protein p38MAPK, which activates p53 and leads to apoptosis in liver cancer cells by regulating Fas protein dynamics.
  • Treatments with SAC showed a normalization of cell cycling and increased apoptosis, while blocking p38MAPK undermined the effectiveness of SAC, suggesting that the p38MAPK-p53 pathway is crucial for its anti-cancer effects.

Article Abstract

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.

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http://dx.doi.org/10.1002/tox.22764DOI Listing

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