Pharmacological inhibition of PI3K/AKT activity by deguelin to treat oral cancers

Deguelin is a very potential, natural plant-derived drug which can suppress cancer cell growth. The mechanism is to suppress the activity of p-AKT, which is proven to over express in many cancer cell types, as human bronchial epithelial (HBE), colon cancer, acute myeloid leukemia (AML), NSCLC, breast cancer and cutaneous squamous cell. After treating deguelin, it gets good efficacy in suppressing cancer cells. But the function of deguelin is not proven in oral cancer therapy research, and how deguelin, AKT inhibitor, suppresses the amplification of oral cancer. We found it had high correlation with over-expression and oral cancer formation in clinical oral cancer tumor sample. In this study, we determined whether inhibition of PI3K/AKT pathway through pharmacological manipulation enhance inhibiting growth of oral cancer. We used deguelin to treat oral cancer cells and observed whether it changed cell growth rate, resulted in cell apoptosis, influenced cell migration and invasion, and changed gene expression in oral cancer. We found that the growth rate of SAS and Cal27 were decreased after treating them with deguelin. The western blot data showed that endogenous AKT activity was suppressed by deguelin. We used boyden chamber to determine cell invasion potentials and used wound colonization to determine cell migration ability. Our data showed that deguelin could decrease HSC3 and SCC4 migration ability, and it also reduced CA922
and SAS invasion potentials. Furthermore, in synergistic effect experiment, low dose of deguelin and cisplatin enhanced more cell apoptosis and drug sensitivity. We thought deguelin maybe a candidate drug of oral cancer
therapy by reducing cell growth rate, invasion potentials and migration ability.