S-allylmercaptocysteine promotes MAPK inhibitor-induced apoptosis by activating the TGF-β signaling pathway in cancer cells.

Abstract

S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur garlic derivatives, can induce the apoptosis of many types of cancer cells through the MAPK signaling pathway. The TGF-β signaling pathway also plays a pivotal role in the process of oncogenesis, and has a certain crosstalk with the MAPK pathway. In the present study, hepatocellular carcinoma cell line HepG2 with an intact TGF-β signal and colon cancer cell line SW620 with an imperfect TGF-β signal were selected to ascertain whether SAMC induces the apoptosis of cancer cells by TGF-β signaling. In both cell lines treated with MAPK inhibitors and SAMC, an increased apoptosis rate was observed by electron microscopy, TUNEL and flow cytometric assays. Immunohistochemistry and western blot assays showed that SAMC induced the apoptosis of cancer cells by activating TGF-β1, TβRII, p-smad2/3, smad4 and smad7 signals, and promoting Bim expression while decreasing Bcl-2 expression and finally activating the mitochondrial apoptosis pathway proteins caspase-3 and caspase-9 in the HepG2 cell line. In contrast, in the SW620 cell line, the apoptosis induced by SAMC only affected TGF-β1 and smad7 signals, and promoted the expression of Bax and Bad and finally activated the mitochondrial apoptosis pathway protein caspase-9. When we compare the apoptosis rate in both cell lines, a significantly lower apoptosis rate was noted in the SW620 cell line than the rate noted in the HepG2 cell line. In summary, SAMC induces the apoptosis of cancer cells by activating the TGF-β signaling pathway, after MAPK signaling is inhibited.

• Authors: Dandan Tong, Hui Qu, Xiangning Meng, Yang Jiang, Duanyang Liu, Shengqian Ye, He Chen, Yan Jin, Songbin Fu, Jingshu Geng
• Journal: Oncology reports (Oncol Rep) Vol. 32 Issue 3 Pg. 1124-32 (Sep 2014) ISSN: 1791-2431 [Electronic] Greece
• PMID: 24970681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Kinase Inhibitors
• S-allylmercaptocysteine
• Transforming Growth Factor beta
• Cysteine

Topics

• Apoptosis
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cysteine (analogs & derivatives, pharmacology)
• Drug Synergism
• Gene Expression Regulation, Neoplastic (drug effects)
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Protein Kinase Inhibitors (pharmacology)
• Signal Transduction (drug effects)
• Transforming Growth Factor beta (metabolism)