Document Detail


Green tea catechins augment the antitumor activity of doxorubicin in an in vivo mouse model for chemoresistant liver cancer.
MedLine Citation:
PMID:  20514403     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Green tea catechins have been reported to have antitumor activity. The objective of this study was to examine the effect of catechins on the antitumor efficacy of doxorubicin (DOX) in a murine model for chemoresistant hepatocellular carcinoma (HCC). Epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) are the most abundant polyphenolic compounds in green tea. Here, we show that ECG or EGCG at higher doses had a slight inhibitory effect on cell proliferation in the resistant human HCC cell line BEL-7404/DOX in vitro and in vivo, whereas the administration of DOX with these compounds at lower doses significantly inhibited HCC cell proliferation in vitro and hepatoma growth in a xenograft mouse model, compared with treatment with either agent alone at the same dose. Furthermore, the administration of DOX in combination with ECG or EGCG markedly enhanced intracellular DOX accumulation, which implies that the catechins inhibited P-glycoprotein (P-gp) efflux pump activity. Consistent with these results, the intracellular retention of rhodamine 123, a P-gp substrate, was increased and the level of P-gp was decreased in cells concurrently treated with DOX and ECG or EGCG. EGCG increased topo II expression, but did not alter GST protein levels in tumor xenografts. The expression of MDR1 and HIF-1alpha mRNA was obviously reduced, whereas MRP1 and LRP expression was not changed significantly. These data suggest that tea catechins at non-toxic doses can augment DOX-induced cell killing and sensitize chemoresistant HCC cells to DOX. The chemosensitizing effect of catechins may occur directly or indirectly by reversal of multidrug resistance, involving the suppression of MDR1 expression, or by enhancement of intracellular DOX accumulation, involving inhibition of P-gp function.
Authors:
Gang Liang; Anzhou Tang; Xiaozhen Lin; Li Li; Su Zhang; Zhiming Huang; Haihua Tang; Qingdi Quentin Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  37     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-01     Completed Date:  2010-09-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  111-23     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, School of Preclinical Sciences, Guangxi Medical University, Nanning 530021, P.R. China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Carcinoma, Hepatocellular / drug therapy*,  pathology
Catechin / administration & dosage*,  pharmacology*
Doxorubicin / administration & dosage*
Drug Resistance, Neoplasm / drug effects
Drug Synergism
Female
Humans
Liver Neoplasms, Experimental / drug therapy*,  pathology
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Models, Biological
Tea / chemistry
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Tea; 154-23-4/Catechin; 23214-92-8/Doxorubicin

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