Loading...
|
Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/3065
|
| Title: | Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53 |
| Authors: | Ho, TF;Ma, CJ;Lu, CH;Tsai, YT;Wei, YH;Chang, JS;La, JK;Cheuh, PJ;Yeh, CT;Tang, PC;Chang, JHT;Ko, JL;Liu, FS;Yen, HCE;Chang, CC |
| Contributors: | National Institute of Cancer Research |
| Abstract: | 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 PAR-P 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. |
| Keywords: | Pharmacology & Pharmacy;Toxicology |
| Date: | 2007-12-15 |
| Relation: | Toxicology and Applied Pharmacology. 2007 Dec;225(3):318-328. |
| Link to: | http://dx.doi.org/10.1016/j.taap.2007.08.007 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0041-008X&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000251535000010 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=36448934493 |
| Appears in Collections: | [其他] 期刊論文
|
Files in This Item:
| File |
Description |
Size | Format | |
|---|
| 000251535000010.pdf | | 806Kb | Adobe PDF | 708 | View/Open |
|
All items in NHRI are protected by copyright, with all rights reserved.
|
