Alpha-Lipoic Acid Inhibits Human Hepatoma Cell Proliferation By Grb2-Mediated Downregulation Of Egfr Activity

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LABackground: It has been reported that α-Lipoic acid (α-LA) as a naturally occurring anti-oxidant, suppresses the growth of hepatoma cells, but the mechanisms remains unclear.Aims: To investigated whether α-LA inhibited hepatoma cells proliferation through EGFR-Grb2.Methods and Results: The results showed that Hu7, Bel7402 and HepG2 proliferation were dramatically decreased after α-LA (2 mM) treatment for 24 and 48 hours, which were measured by CCK8 assay. Moreover, phosphorylation levels of EGFR was decreased by α-LA treatment, and its associated with an inhibition in cell-cycle transition. Next, we found that growth factor receptor bound protein 2 (Grb2), which is adaptor protein, was also significantly reduced by RT-PCR and western blot after α-LA treatment at 24 and 48 hours. Consistent with previous report, silenced of Grb2 dramatically blocked cell proliferation. To test whether the downregulation of Grb2 mediates α-LA induced proliferation inhibition, Grb2 was transfected into hepatoma cells to recover the reduction of Grb2 induced by α-LA. It was showed that overexpression of Grb2 also successfully inhibited α-LA induced decrease of cell proliferation. In addition, the data showed that phosphorylation levels of ERK1/2 was decreased by cell treated with α-LA. These results suggested that the Grb2 through binds to phosphorylated site in EGFR medicated α-LA suppress cell proliferation.Conclusion: Our study showed α-LA inhibited cell proliferation through Grb2 suppressed phosphorylation levels of EGFR, ERK1/2 was involved in this pathway.Citation Format: Lan Yang, Yuntao Lin, Ya Wen, XiaoJuan Sun. α-Lipoic acid inhibits human hepatoma cell proliferation by Grb2-mediated downregulation of EGFR activity. [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 828.