[11'-Deoxyverticillin A induces caspase-dependent cell apoptosis in PC3M cells].
Recent years, the incidence and mortality of prostate cancer have increased dramatically in China. At earlier stages, most diagnosed prostate cancers are responsive to androgen depletion treatment, yet, nearly all patients will eventually progress to metastatic androgen-independent prostate cancer (AIPC), which still has no effective therapeutic method or drug to deal with. 11'-Deoxyverticillin A (C42) belongs to the family of epipolythiodioxopiperazines (ETPs), an interesting class of fungal toxins that inhibit farnesyl transferase. Compounds holding such a property have been explored as putative anticancer agents. In this study, using PC3M cells, an AIPC cell line, we investigated the effect of the compound on apoptosis and explored the underlying mechanism. It revealed that C42 markedly enhanced the activity of caspase-3/7 and increased the accumulation of the cleaved PARP, all of which are the markers of apoptosis. It also revealed that C42 either decreased cell viability or inhibited the growth of PC3M cells. Moreover, we observed that the loss of cell viability and cell growth inhibition induced by C42 were both time- and dosage dependent. Taken together, we indicated that C42 can induce caspase-dependent apoptosis in AIPC cells, and the results presented here will broaden our knowledge about the molecular mechanisms by which C42 exerts its anticancer activity, and future work in this direction may provide valuable information in the development of these compounds into effective cancer therapeutic strategies against androgen-independent prostate cancer.
Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Yingdi
Y
Shi
Yingqiu
Y
Zhang
Yangxiao
Y
Ni
Guoli
G
Shi
Huaiyi
H
Yang
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D004220:Disulfides / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D009183:Mycotoxins / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*
D004220:Disulfides; D009183:Mycotoxins; D010879:Piperazines; D051231:Farnesyltranstransferase; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; C540279:11,11'-dideoxyverticillin A