Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/38524
標題: Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53
作者: Ho, T.F.
顏宏真
Ma, C.J.
Lu, C.H.
Tsai, Y.T.
Wei, Y.H.
Chang, J.S.
La, J.K.
Cheuh, P.J.
Yeh, C.T.
Tang, P.C.
Chang, J.H.T.
Ko, J.L.
Liu, F.S.
Yen, H.C.E.
Chang, C.C.
闕斌如
張嘉哲
唐品琦
關鍵字: undecylprodigiosin (UP)
breast cancer
apoptosis
z-VAD.fmk
poly
(ADP-ribose) polymerase (PARP)
Bcl-2 family
p53
nf-kappa-b
prodigiosin 25-c
bcl-2 family
cancer-cells
induction
death
proliferation
protein
gene
supplementation
期刊/報告no:: Toxicology and Applied Pharmacology, Volume 225, Issue 3, Page(s) 318-328.
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 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. (c) 2007 Elsevier Inc. All rights reserved.
URI: http://hdl.handle.net/11455/38524
ISSN: 0041-008X
文章連結: http://dx.doi.org/10.1016/j.taap.2007.08.007
Appears in Collections:生命科學系所

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