Abstract 1326: 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranoside a novel c-Myc inhibitor induces GNMT expression and apoptosis in hepatocellular carcinoma

Abstract

Abstract 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranoside (PGG) possesses potent anticancer activities. We identified PGG as GNMT inducer by using GNMT based drug screening platform. In this study we aimed to find the mechanism of action of PGG in hepatocellular carcinoma (HCC). We used microarray analysis to identify the differently expressed genes induced by PGG. Microarray experiment showed that c-Myc was involved in all detected pathways in enrichment analysis. PGG suppressed c-Myc mRNA and protein expression in Huh7 and Hep G2 cells. Knocked-down of c-Myc resulted in significant induction of GNMT promoter activity and endogenous GNMT mRNA expression. Furthermore, overexpression of c-Myc significantly inhibited GNMT promoter activity and endogenous GNMT protein expression. Moreover, PGG not only inhibited c-Myc mRNA expression but also induced degradation of c-Myc protein in Huh7 cells. Finally we found that PGG induces apoptosis in Huh7 cells. Taken together, PGG is a novel c-Myc inhibitor and induces GNMT through c- Myc modulation in HCC. Our results also suggest that PGG may potentially be a good drug candidate for HCC and c-Myc overexpressing cancers. Citation Format: Rajni Kant, Chia Hung Yen, Chung Kuang Lu, Chien Yi Tung, Yi-Ming Chen. 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranoside a novel c-Myc inhibitor induces GNMT expression and apoptosis in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1326.