Abstract |
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.
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Authors | Hyo Jung Nam, Jin Ku Kang, Jong Soo Chang, Min Soo Lee, Seung Taek Nam, Hyun Woo Jung, Sung-Kuk Kim, Eun-Mi Ha, Heon Seok, Seung Woo Son, Young Joo Park, Ho Kim |
Journal | Journal of microbiology and biotechnology
(J Microbiol Biotechnol)
Vol. 22
Issue 1
Pg. 50-7
(Jan 2012)
ISSN: 1738-8872 [Electronic] Korea (South) |
PMID | 22297219
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bacterial Toxins
- Enterotoxins
- tcdA protein, Clostridium difficile
- Phospholipase C gamma
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Topics |
- Animals
- Apoptosis
- Bacterial Toxins
(toxicity)
- Cell Transformation, Neoplastic
- Cells, Cultured
- Enterotoxins
(toxicity)
- Fibroblasts
(drug effects, metabolism)
- Gene Expression Profiling
- Mitosis
- Phospholipase C gamma
(biosynthesis, genetics)
- Rats
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