Cells transformed by PLC-gamma 1 overexpression are highly sensitive to clostridium difficile toxin A-induced apoptosis and mitotic inhibition.
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.
Department of Life Science, College of Natural Science, Daejin University, Pochen, Korea.
Hyo Jung
HJ
Nam
Jin Ku
JK
Kang
Jong Soo
JS
Chang
Min Soo
MS
Lee
Seung Taek
ST
Nam
Hyun Woo
HW
Jung
Sung-Kuk
SK
Kim
Eun-Mi
EM
Ha
Heon
H
Seok
Seung Woo
SW
Son
Young Joo
YJ
Park
Ho
H
Kim
D000818:Animals; D017209:Apoptosis; D001427:Bacterial Toxins / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004768:Enterotoxins / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D008938:Mitosis; D051966:Phospholipase C gamma / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats
D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; D051966:Phospholipase C gamma