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Cells Transformed by PLC-Gamma 1 Overexpression are Highly Sensitive to Clostridium difficile Toxin A-Induced Apoptosis and Mitotic Inhibition
1Department of Life Science, College of Natural Science, Daejin University, Pochen, Korea, 2College of Pharmacy, Catholic University of Daegu, Gyeogsan-Si, Gyeongbuk, Korea, 3Department of Medical Engineering, Jungwon University, Goesan, Chungcheongbukdo, Korea, 4Suzhou Singapore International School, Suzhou Industrial Park, Jiangsu, P.R. China, 5Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
J. Microbiol. Biotechnol. 2012; 22(1): 50-57
Published January 28, 2012 https://doi.org/10.4014/jmb.1107.07018
Copyright © The Korean Society for Microbiology and Biotechnology.
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J. Microbiol. Biotechnol. 2012; 22(1): 50-57
Published online January 28, 2012 https://doi.org/10.4014/jmb.1107.07018
Copyright © The Korean Society for Microbiology and Biotechnology.
Cells Transformed by PLC-Gamma 1 Overexpression are Highly Sensitive to Clostridium difficile Toxin A-Induced Apoptosis and Mitotic Inhibition
Hyo Jung Nam 1, Jin Ku Kang 1, Jong Soo Chang 1, Min Soo Lee 1, Seung Taek Nam 1, Hyun Woo Jung 1, Sung-Kuk Kim 1, Eun-Mi Ha 2, Heon Seok 3, Seung Woo Son 4, Young Joo Park 5 and Ho Kim 1*
1Department of Life Science, College of Natural Science, Daejin University, Pochen, Korea, 2College of Pharmacy, Catholic University of Daegu, Gyeogsan-Si, Gyeongbuk, Korea, 3Department of Medical Engineering, Jungwon University, Goesan, Chungcheongbukdo, Korea, 4Suzhou Singapore International School, Suzhou Industrial Park, Jiangsu, P.R. China, 5Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
Abstract
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.
Keywords: phospholipase c gamma1, bacterial toxin, cancer, apoptosis, clostridium difficile, mitotic inhibition
