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

Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53. Research Abstract Details 

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Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53. Abstract Text:

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,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,

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-X(L), 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.

Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53. Publishing Authors By Initials

TF Ho,CJ Ma,CH Lu,YT Tsai,YH Wei,JS Chang,JK Lai,PJ Cheuh,CT Yeh,PC Tang,J Tsai Chang,JL Ko,FS Liu,HE Yen,CC Chang,TF Ho,CJ Ma,CH Lu,YT Tsai,YH Wei,JS Chang,JK Lai,PJ Cheuh,CT Yeh,PC Tang,J Tsai Chang,JL Ko,FS Liu,HE Yen,CC Chang,

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Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Toxicology and applied pharmacology

VOLUME: 225

Page Numbers: 318-28

Journal Abbreviation: Toxicol. Appl. Pharmacol.

ISSN: 0041-008X

DAY: 22

MONTH: 08

YEAR: 2007

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

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LANGUAGE: eng

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AFFILIATION: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.

Country: United States

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MEDLINETA: Toxicol Appl Pharmacol

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