請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/40278
標題: Prodigiosin down-regulates survivin to facilitate paclitaxel sensitization in human breast carcinoma cell lines
作者: Ho, T.F.
張嘉哲
Peng, Y.T.
Chuang, S.M.
Lin, S.C.
Feng, B.L.
Lu, C.H.
Yu, W.J.
Chang, J.S.
Chang, C.C.
莊秀美
關鍵字: Prodigiosin
Survivin
Paclitaxel
Apoptosis
Breast cancer
anticancer agent prodigiosin
lung-cancer cells
induced apoptosis
targeting survivin
microtubule dynamics
gene-expression
ovarian-cancer
tumor-cells
resistance
taxol
期刊/報告no:: Toxicology and Applied Pharmacology, Volume 235, Issue 2, Page(s) 253-260.
摘要: Prodigiosin is a bacterial metabolite with potent anticancer activity, which is attributed to its proapoptotic effect selectively active in malignant cells. Still, the molecular mechanisms whereby prodigiosin induces apoptosis remain largely unknown. In particular, the role of suivivin, a vital inhibitor of apoptosis, in prodigiosin-induced apoptosis has never been addressed before and hence was the primary goal of this study. Our results showed that prodigiosin close-dependently induced down-regulation of survivin in multiple breast carcinoma cell lines, including MCF-7, T-47D and MDA-MB-231. This down-regulation is mainly regulated at the level of transcription, as prodigiosin reduced the levels of both survivin mRNA and survivin promoter activity but failed to rescue survivin expression when proteasome-mediated degradation is abolished. Importantly, overexpression of survivin rendered cells more resistant to prodigiosin, indicating all essential role of survivin down-regulation in prodigiosin-induced apoptosis. In addition, we found that prodigiosin synergistically enhanced cell death induced by paclitaxel, a chemotherapy drug known to up-regulate survivin that ill turn confers its own resistance. This paclitaxel sensitization effect of prodigiosin is ascribed to the lowering of survivin expression, because prodigiosin was shown to counteract survivin induction by paclitaxel and, notably, the sensitization effect was severely abrogated in cells that overexpress survivin. Taken together, our results argue that down-regulation of survivin is all integral component mediating prodigiosin-induced apoptosis in human breast cancer cells, and further suggest the potential of prodigiosin to sensitize anticancer drugs, including paclitixel, in the treatment of breast cancer. (C) 2008 Elsevier Inc. All rights reserved.
URI: http://hdl.handle.net/11455/40278
ISSN: 0041-008X
文章連結: http://dx.doi.org/10.1016/j.taap.2008.12.009
顯示於類別:生物醫學研究所

文件中的檔案:
沒有與此文件相關的檔案。


在 DSpace 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。