Synergistic anti-cancer mechanisms of curcumin and paclitaxel for growth inhibition of human brain tumor stem cells and LN18 and U138MG cells.
Synergistic anti-cancer mechanisms of curcumin and paclitaxel for growth inhibition of human brain tumor stem cells and LN18 and U138MG cells.
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DOI：
10.1016/j.neuint.2012.08.002
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发表时间：
2012-12
影响因子：
4.2
通讯作者：
Ray, Swapan K.
中科院分区：
文献类型：
--
作者：
Hossain, Md Motarab;Banik, Naren L.;Ray, Swapan K.
Glioblastoma, the deadliest brain tumor in humans, responds poorly to conventional chemotherapeutic agents because of existence of highly chemoresistant human brain tumor stem cells (HBTSC). An effective therapeutic strategy is urgently needed to target HBTSC as well as other glioblastoma cells. We explored synergistic efficacy of a low dose of curcumin (CCM) and a low dose of paclitaxel (PTX) in HBTSC and human glioblastoma LN18 (p53 mutant and PTEN proficient) and U138MG (p53 mutant and PTEN mutant) cells. The highest expression of the cancer stem cell markers aldehyde dehydrogenase 1 (ALDH1) and CD133 occurred in HBTSC when compared with LN18 and U138MG cells. Combination of 20 µM CCM and 10 nM PTX worked synergistically and more effectively than either drug alone in decreasing viability in all cells. Combination of CCM and PTX was highly effective in inducing both morphological and biochemical features of apoptosis. Apoptosis required activation of caspase-8, cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, and mitochondrial release of cytochrome c, Smac, and apoptosis-inducing factor (AIF). Phosphorylation of Bcl-2 following combination therapy appeared to promote Bax homodimerization and mitochondrial release of proapoptotic factors into the cytosol. Increases in activities cysteine proteases confirmed the completion of apoptotic process. Combination therapy inhibited invasion of cells, reduced expression of survival and proliferation factors and also angiogenic factors, and prevented HBTSC, LN18, and U138MG cells from promoting network formation. Collectively, the combination of CCM and PTX worked as a promising therapy for controlling the growth of HBTSC and other glioblastoma cells.
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影响因子：
11.2
作者：
Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
通讯作者：
Boman BM
影响因子：
11.2
作者：
Chesler, Louis;Goldenberg, David D.;Weiss, William A.
通讯作者：
Weiss, William A.
影响因子：
3.9
作者：
Das, Arabinda;Banik, Naren L.;Ray, Swapan K.
通讯作者：
Ray, Swapan K.
影响因子：
4.8
作者：
Pathan, N;Aime-sempe, C;Reed, JC
通讯作者：
Reed, JC
DOI：
10.1073/pnas.92.10.4507
发表时间：
1995-05-09
影响因子：
11.1
作者：
HALDAR, S;JENA, N;CROCE, CM
通讯作者：
CROCE, CM