Synergistic Anti-Cancer Effects of Grape Seed Extract and Conventional Cytotoxic Agent Doxorubicin Against Human Breast Carcinoma Cells Girish Sharma Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO, USA These authors contributed equally to this work Anil K. Tyagi Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO, USA These authors contributed equally to this work Rana P. Singh Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO, USA Daniel C.F. Chan Department of Medicine, Division of Medical Oncology, University of Colorado Health Sciences Center, Denver, CO, USA University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, CO, USA Rajesh Agarwal Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO, USA University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, CO, USA Abstract 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 µg/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 µg/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 µg/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 ~ 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. Breast Cancer Research and Treatment 85 (1): 1-12, May 2004 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.