Tong Dandan, Qu Hui, Meng Xiangning, Jiang Yang, Liu Duanyang, Ye Shengqian, Chen He, Jin Yan, Fu Songbin, Geng Jingshu
Department of Pathology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Department of Pediatrics, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Oncol Rep. 2014 Sep;32(3):1124-32. doi: 10.3892/or.2014.3295. Epub 2014 Jun 26.
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.
S-烯丙基巯基半胱氨酸（SAMC）是水溶性有机硫大蒜衍生物之一，可通过丝裂原活化蛋白激酶（MAPK）信号通路诱导多种癌细胞凋亡。转化生长因子-β（TGF-β）信号通路在肿瘤发生过程中也起着关键作用，并且与MAPK通路存在一定的相互作用。在本研究中，选择具有完整TGF-β信号的肝癌细胞系HepG2和具有不完整TGF-β信号的结肠癌细胞系SW620，以确定SAMC是否通过TGF-β信号诱导癌细胞凋亡。在用MAPK抑制剂和SAMC处理的两种细胞系中，通过电子显微镜、TUNEL和流式细胞术检测观察到凋亡率增加。免疫组织化学和蛋白质印迹分析表明，SAMC通过激活TGF-β1、TβRII、p-smad2/3、smad4和smad7信号诱导癌细胞凋亡，并促进Bim表达，同时降低Bcl-2表达，最终激活HepG2细胞系中的线粒体凋亡通路蛋白caspase-3和caspase-9。相反，在SW620细胞系中，SAMC诱导的凋亡仅影响TGF-β１和smad7信号，并促进Bax和Bad的表达，最终激活线粒体凋亡通路蛋白caspase-9。当比较两种细胞系的凋亡率时，发现SW620细胞系的凋亡率明显低于HepG2细胞系。总之，在MAPK信号被抑制后，SAMC通过激活TGF-β信号通路诱导癌细胞凋亡。
