Sulforaphane Inhibits Growth of Human Breast Cancer Cells and Augments the Therapeutic Index of the Chemotherapeutic Drug, Gemcitabine

Abstract

Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking orreversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategiesto reduce cancer related death. One such promising chemopreventive agent which has attracted considerableattention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. Thepresent study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent,gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the resultsby nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 and COX-2on treatment of these cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose- andtime-dependent manner via an apoptotic mode of cell death. In addition, a combinational treatment of SFNand gemcitabine on MCF-7 cells resulted in growth inhibition in a synergistic manner with a combination index(CI)<1. Notably, SFN was found to significantly downregulate the expression of Bcl-2, an anti-apoptotic gene, andCOX-2, a gene involved in inflammation, in a time-dependent manner. These results indicate that SFN inducesapoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively.The combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and minimize the toxicityto normal cells. Taken together, SFN may be a potent anti-cancer agent for breast cancer treatment.