Document Detail

Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells.
MedLine Citation:
PMID:  15039593     Owner:  NLM     Status:  MEDLINE    
With an approach to enhance the efficacy of chemotherapy agents against breast cancer treatment, here, we investigated the anti-cancer effects of grape seed extract (GSE) and doxorubicin (Dox), either alone or in combination, in estrogen receptor-positive MCF-7 and receptor-negative MDA-MB468 human breast carcinoma cells. GSE (25-200 micro g/ml) treatment of cells resulted in 16-72% growth inhibition and 9-33% cell death, in a dose- and a time-dependent manner. In other studies, Dox (10-100 nM) treatment showed 23-96% growth inhibition and 10-55% cell death. Based on these results, several combinations of GSE (25-100 micro g/ml) with Dox (10-75 nM) were next assessed for their synergistic, additive and/or antagonistic efficacy towards cell growth inhibition and death. In both MCF-7 and MDA-MB468 cells, a combination of 100 micro g/ml GSE with 25-75 nM Dox treatment for 48 h showed a strong synergistic effect [combination index (CI) < 0.5] in cell growth inhibition, but mostly an additive effect (CI approximately 1) in cell death. In cell-cycle progression studies, GSE plus Dox combination resulted in a moderate increase in G1 arrest in MCF-7 cells compared to each agent alone. GSE plus Dox combination showed a very strong and significant G1 arrest in MDA-MB468 cells when compared with Dox alone, however, it was less than that observed with GSE alone. In quantitative apoptosis studies, GSE and Dox alone and in combination showed comparable apoptotic death of MCF-7 cells, however, a combination of the two was inhibitory to Dox induced apoptosis in MDA-MB468 cells. This was further confirmed in another estrogen receptor-negative MDA-MB231 cell line, in which GSE and Dox combination strongly inhibited cell growth but did not show any increase in apoptotic cell death caused by Dox. Together, these results suggest a strong possibility of synergistic efficacy of GSE and Dox combination for breast cancer treatment, independent of estrogen receptor status of the cancer cell.
Girish Sharma; Anil K Tyagi; Rana P Singh; Daniel C F Chan; Rajesh Agarwal
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Breast cancer research and treatment     Volume:  85     ISSN:  0167-6806     ISO Abbreviation:  Breast Cancer Res. Treat.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-03-24     Completed Date:  2004-06-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8111104     Medline TA:  Breast Cancer Res Treat     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1-12     Citation Subset:  IM    
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
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MeSH Terms
Antineoplastic Agents / therapeutic use*
Breast Neoplasms / drug therapy*
Cell Death / drug effects
Cell Division / drug effects
Cell Line, Tumor
Doxorubicin / therapeutic use*
Drug Synergism
Plant Extracts / therapeutic use*
Receptors, Estrogen
Grant Support
P30 CA46934-14S1/CA/NCI NIH HHS
Reg. No./Substance:
0/Antineoplastic Agents; 0/Plant Extracts; 0/Receptors, Estrogen; 23214-92-8/Doxorubicin

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