Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53

Tsing Fen Ho, Chieh Ju Ma, Chien Hsing Lu, Yo Ting Tsai, Yu Hong Wei, Jo Shu Chang, Jun Kai Lai, Pin Ju Cheuh, Chi Tai Yeh, Pin Chi Tang, Jinghua Tsai Chang, Jiunn Liang Ko, Fu Shing Liu, Hungchen E. Yen, Chia Che Chang

研究成果: Article同行評審

34 引文 斯高帕斯(Scopus)

摘要

Undecylprodigiosin (UP) is a bacterial bioactive metabolite produced by Streptomyces and Serratia. In this study, we explored the anticancer effect of UP. Human breast carcinoma cell lines BT-20, MCF-7, MDA-MB-231 and T47D and one nonmalignant human breast epithelial cell line, MCF-10A, were tested in this study. We found that UP exerted a potent cytotoxicity against all breast carcinoma cell lines in a dose- and time-dependent manner. In contrast, UP showed limited toxicity to MCF-10A cells, indicating UP's cytotoxic effect is selective for malignant cells. UP's cytotoxic effect was due to apoptosis, as confirmed by positive TUNEL signals, annexin V-binding, caspase 9 activation and PARP cleavage. Notably, UP-induced apoptosis was blocked by the pan-caspase inhibitor z-VAD.fmk, further indicating the involvement of caspase activity. Moreover, UP caused a marked decrease of the levels of antiapoptotic BCL-XL, Survivin and XIAP while enhancing the levels of proapoptotic BIK, BIM, MCL-1S and NOXA, consequently favoring induction of apoptosis. Additionally, we found that cells with functional p53 (MCF-7, T47D) or mutant p53 (BT-20, MDA-MB-231) were both susceptible to UP's cytotoxicity. Importantly, UP was able to induce apoptosis in MCF-7 cells with p53 knockdown by RNA interference, confirming the dispensability of p53 in UP-induced apoptosis. Overall, our results establish that UP induces p53-independent apoptosis in breast carcinoma cells with no marked toxicity to nonmalignant cells, raising the possibility of its use as a new chemotherapeutic drug for breast cancer irrespective of p53 status.

原文English
頁(從 - 到)318-328
頁數11
期刊Toxicology and Applied Pharmacology
225
發行號3
DOIs
出版狀態Published - 2007 十二月 15

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

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