Green tea polyphenol EGCG suppresses osteosarcoma cell growth through upregulating miR-1.

Abstract

(-)-Epigallocatechin-3-gallate (EGCG), the most abundant and active polyphenol in green tea, has been demonstrated to have anticancer effects in a wide variety of human cancer. MicroRNAs (miRNAs) are a class of short noncoding RNAs and play important role in gene regulation and are critically involved in the pathogenesis and progression of human cancer. This study aims to investigate the effects of EGCG on osteosarcoma (OS) cells and elucidate the underlying mechanism. Cellular function assays revealed that EGCG inhibited cell proliferation, induced cell cycle arrest and promoted apoptosis of OS cells in vitro, and also inhibited the growth of transplanted tumors in vivo. By miRNA microarray and RT-qPCR analysis, miR-1 was found to be significantly upregulated in MG-63 and U-2OS treated by EGCG in dose- and time-dependent manners, and miR-1 downregulation by inhibitor mimics attenuated EGCG-induced inhibition on cell growth of OS cells. We also confirmed that miR-1 was also frequently decreased in clinical OS tumor tissues. Moreover, both EGCG and miR-1 mimic inhibited c-MET expression, and combination treatment with EGCG and c-MET inhibitor (crizotinib) had enhanced inhibitory effects on the growth of MG-63 and U-2OS cells. Taken together, these results suggest that EGCG has an anticancer effect on OS cells, at least partially, through regulating miR-1/c-MET interaction.