Journal
ONCOLOGY REPORTS
Volume 32, Issue 3, Pages 1124-1132Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2014.3295
Keywords
S-allylmercaptocysteine; apoptosis; TGF-beta pathway; smad; Bim
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Funding
- National Natural Science Foundation of China [81372785]
- Natural Science Foundation of Heilongjiang [D200921, QC2009C29]
- Opening Project of the Key Laboratory of Medical Genetics (Harbin Medical University), Heilongjiang Higher Education Institutions
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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-beta 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-beta signal and colon cancer cell line SW620 with an imperfect TGF-beta signal were selected to ascertain whether SAMC induces the apoptosis of cancer cells by TGF-beta 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-beta, T beta RII, 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-beta 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-beta signaling pathway, after MAPK signaling is inhibited.
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