Combination of Epigallocatechin-3-gallate and Silibinin: A Novel Approach for Targeting Both Tumor and Endothelial Cells

Abstract

Despite promising benefits, anti-angiogenic strategies have revealed several drawbacks, which necessitate development of novel approaches in cancer therapy strategies including non-small-cell lung cancer, as one of the leading causes of cancer death, all over the world. Combination of flavonoids could be a safe and effective option to synergize their impact on mechanisms controlling tumor angiogenesis. In this study, we have investigated the plausible synergism of epigallocatechin-3-gallate (EGCG) and silibinin on endothelial cells, for the first time. Cell viability and migration were evaluated by survival and wound healing assays, respectively. Then, we assessed the expression of <i>VEGF</i>, <i>VEGFR</i>2, and miR-17-92 cluster using real-time polymerase chain reaction in endothelial-tumor cell and endothelial-fibroblast coculture models. EGCG ± silibinin suppressed endothelial and lung tumor cell migration in lower than 50% toxic doses. <i>VEGF</i>, <i>VEGFR</i>2, and pro-angiogenic members of the miR-17-92 cluster were downregulated upon treatments. Specifically, the combination treatment upregulated an anti-angiogenic member of the cluster, miR-19b. Our data provides evidence to utilize the EGCG and silibinin combination as a novel approach to target tumor angiogenesis in the future.