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KMID : 0545120120220010050
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Journal of Microbiology and Biotechnology
2012 Volume.22 No. 1 p.50 ~ p.57
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Cells Transformed by PLC-Gamma 1 Overexpression are Highly Sensitive to Clostridium difficile Toxin A-Induced Apoptosis and Mitotic Inhibition
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Nam Hyo-Jung
Kang Jin-Ku
Chang Jong-Soo
Lee Min-Soo
Nam Seung-Taek
Jung Hyun-Woo
Kim Sung-Kuk
Ha Eun-Mi
Seok Heon
Son Seung-Woo
Park Young-Joo
Kim Ho
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Abstract
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Phospholipase C-γl (PLC-γl) expression is associated with cellular transformation. Notably, PLC-γ 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.
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KEYWORD
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phospholipase c gamma1, bacterial toxin, cancer, apoptosis, clostridium difficile, mitotic inhibition
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