Document Detail


Synergistic anti-cancer mechanisms of curcumin and paclitaxel for growth inhibition of human brain tumor stem cells and LN18 and U138MG cells.
MedLine Citation:
PMID:  22910273     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 20μM CCM and 10nM 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 pro-apoptotic factors into the cytosol. Increases in activities of 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.
Authors:
Motarab Hossain; Naren L Banik; Swapan K Ray
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-13
Journal Detail:
Title:  Neurochemistry international     Volume:  61     ISSN:  1872-9754     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-26     Completed Date:  2013-06-05     Revised Date:  2013-12-05    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  1102-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Blotting, Western
Cell Line
Curcumin / administration & dosage,  pharmacology*
Drug Synergism
Glioblastoma / pathology*
Humans
Microscopy, Fluorescence
Neoplastic Stem Cells / drug effects*
Paclitaxel / administration & dosage,  pharmacology*
Grant Support
ID/Acronym/Agency:
R01 NS065456/NS/NINDS NIH HHS; R01 NS65456/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 33069-62-4/Paclitaxel; IT942ZTH98/Curcumin
Comments/Corrections

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