Abstract P6-14-14: Concerted Anti-Tumor/Radiosentizing Effect of Epigallocatechin Gallate, Resveratrol and Genistein by Targeting Tumor Invasion and Metastasis Molecules in Human Breast Cancer Cells

Abstract

Abstract Accomplishing the desired anti-tumor efficacy with individual dietary phytochemicals is clinically unachievable. This is due to the existence of converging and diverging pathways spanning the complex metabolic networks in cancer cells. This complexity demands the development of a multi-component approach with physiological doses of phytochemicals that could be used as “deliverable” anti-cancer agent. To address this concern, we investigated the synergistic efficacy of Genistein (GEN), Epigallocatechin gallate (EGCG) and Resveratrol (RES) in mitigating cancer progression. Human breast adenocarcinoma cells (MCF-7 and MDA-MB-231) were treated with physiological concentration of GEN, EGCG, RES, individually or all three together (GER). In parallel cultures cells were treated with GER and either exposed to radiation (2Gy;IR) or treated with β-estradiol (≥2E, positive control). The trated cells were examined after 24h. In MCF-7 cells, QPCR profiling of 93 tumor invasion and metastasis molecules revealed that EGCG, RES and GEN significantly (≥2 fold) induced 23, 36, 22 genes and completely suppressed 61, 40 and 64 genes respectively as stand-alone compounds. Conversely, GER completely knocked down the transcription of 82 genes, while another 9 genes were maintained at baseline level. More importantly, GER significantly inhibited 75 and 63 genes in ≥2E and IR exposed MCF-7 cells. Interestingly, in highly metastatic MDA-MB-231 cells, EGCG, RES, GEN significantly induced 17, 19, 2 genes and completely suppressed 41, 26 and 57 genes respectively as stand-alone compounds. Conversely, GER completely suppressed 67 genes while another 17 genes were maintained at baseline level. To that end, GER significantly inhibited 57 and 59 genes and maintained 16 genes at basal level in ≥2E and IR exposed MCF-7 cells. Taken together, these data evidently exhibit the potential synergestic effect of EGCG, GEN and RES in mitigating breast cancer progression as opposed to their stand alone effect. More importantly, these data strongly suggests that GER potentiates synergistic radiosensitization in these cells and this GER influenced radiosensitization may involve selective targeting of tumor invasion and metastatic transcription. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-14-14.