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S-苄基-半胱氨酸介导人胃癌SGC-7901细胞的细胞周期阻滞和凋亡,这涉及通过p53途径激活线粒体依赖性半胱天冬酶级联反应。

S-benzyl-cysteine-mediated cell cycle arrest and apoptosis involving activation of mitochondrial-dependent caspase cascade through the p53 pathway in human gastric cancer SGC-7901 cells.

作者信息

Sun Hua-Jun, Meng Lin-Yi, Shen Yang, Zhu Yi-Zhun, Liu Hong-Rui

机构信息

Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China E-mail :

出版信息

Asian Pac J Cancer Prev. 2013;14(11):6379-84. doi: 10.7314/apjcp.2013.14.11.6379.

DOI:10.7314/apjcp.2013.14.11.6379
PMID:24377536
Abstract

S-benzyl-cysteine (SBC) is a structural analog of S-allylcysteine (SAC), which is one of the major water- soluble compounds in aged garlic extract. In this study, anticancer activities and the underlying mechanisms of SBC action were investigated and compared these with those of SAC using human gastric cancer SGC-7901 cells. SBC significantly suppressed the survival rate of SGC-7901 cells in a concentration- and time-dependent manner, and the inhibitory activities of SBC were stronger than those of SAC. Flow cytometry revealed that SBC induced G2-phase arrest and apoptosis in SGC-7901 cells. Typical apoptotic morphological changes were observed by Hoechst 33258 dye assay. SBC-treatment dramatically induced the dissipation of mitochondrial membrane potential (Δψm), and enhanced the enzymatic activities of caspase-9 and caspase-3 whilst hardly affecting caspase-8 activity. Furthermore, Western blotting indicated that SBC-induced apoptosis was accompanied by up-regulation of the expression of p53, Bax and the down-regulation of Bcl-2. Taken together, this study suggested that SBC exerts cytotoxic activity involving activation of mitochondrial-dependent apoptosis through p53 and Bax/Bcl-2 pathways in human gastric cancer SGC-7901 cells.

摘要

S-苄基半胱氨酸(SBC)是S-烯丙基半胱氨酸(SAC)的结构类似物,SAC是陈年大蒜提取物中的主要水溶性化合物之一。在本研究中,研究了SBC的抗癌活性及其作用的潜在机制,并使用人胃癌SGC-7901细胞将其与SAC的抗癌活性和作用机制进行了比较。SBC以浓度和时间依赖性方式显著抑制SGC-7901细胞的存活率,且SBC的抑制活性强于SAC。流式细胞术显示,SBC诱导SGC-7901细胞发生G2期阻滞和凋亡。通过Hoechst 33258染色试验观察到典型的凋亡形态学变化。SBC处理显著诱导线粒体膜电位(Δψm)的消散,并增强caspase-9和caspase-3的酶活性,而对caspase-8活性影响不大。此外,蛋白质印迹法表明,SBC诱导的凋亡伴随着p53、Bax表达的上调和Bcl-2表达的下调。综上所述,本研究表明,SBC在人胃癌SGC-7901细胞中通过p53和Bax/Bcl-2途径激活线粒体依赖性凋亡,从而发挥细胞毒性活性。

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