Gomisin G Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing AKT Phosphorylation and Decreasing Cyclin D1

A type of breast Cancer with a defect in three molecular markers such as the Estrogen receptor, Progesterone Receptor, and human epidermal growth factor receptor is called triple-negative breast Cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with Other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC Cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce Apoptosis but drastically inhibited Akt phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in Akt phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing Apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.

AKT; Cell cycle; Cell proliferation; Cyclin D1; Gomisin G; Triple negative breast cancer.