Department of Life Science, College of Natural Science, Daejin University, Pochen, Korea.
J Microbiol Biotechnol. 2012 Jan;22(1):50-7. doi: 10.4014/jmb.1107.07018.
Phospholipase C-γl (PLC-γl) expression is associated with cellular transformation. Notably, PLC-gamma is up-regulated in colorectal cancer tissue and breast carcinoma. Because exotoxins released by Clostridium botulinum have been shown to induce apoptosis and promote growth arrest in various cancer cell lines, we examined here the potential of Clostridium difficile toxin A to selectively induce apoptosis in cells transformed by PLC-γl overexpression. We found that PLC-γl-transformed cells, but not vectortransformed (control) cells, were highly sensitive to C. difficile toxin A-induced apoptosis and mitotic inhibition. Moreover, expression of the proapoptotic Bcl2 family member, Bim, and activation of caspase-3 were significantly up-regulated by toxin A in PLC-γl-transformed cells. Toxin A-induced cell rounding and paxillin dephosphorylation were also significantly higher in PLC-γl-transformed cells than in control cells. These findings suggest that C. difficile toxin A may have potential as an anticancer agent against colorectal cancers and breast carcinomas in which PLC-γl is highly up-regulated.
PLC-γl（磷脂酶 C-γl）的表达与细胞转化有关。值得注意的是，PLC-γ在结直肠癌组织和乳腺癌中上调。由于肉毒梭菌释放的外毒素已被证明能诱导多种癌细胞系凋亡并促进生长停滞，我们在此研究艰难梭菌毒素 A 是否能选择性地诱导 PLC-γl 过表达的细胞凋亡。我们发现，PLC-γl 转化的细胞，而不是载体转化的（对照）细胞，对艰难梭菌毒素 A 诱导的凋亡和有丝分裂抑制高度敏感。此外，在 PLC-γl 转化的细胞中，促凋亡 Bcl2 家族成员 Bim 的表达和 caspase-3 的激活显著上调。毒素 A 诱导的细胞圆化和桩蛋白去磷酸化在 PLC-γl 转化的细胞中也明显高于对照细胞。这些发现表明，艰难梭菌毒素 A 可能具有作为针对结直肠癌和乳腺癌的抗癌剂的潜力，在这些癌症中 PLC-γl 高度上调。
