Diosmetin Induces Apoptosis by Downregulating AKT Phosphorylation via P53 Activation in Human Renal Carcinoma ACHN Cells

Background: Diosmetin (DIOS) is the aglycone of the flavonoid glycoside, diosmin, derived naturally from the leaves of the legume, Olea europaea, and Acacia farnesiana. It has potent anticancer activity against multiple forms of cancers. However, the role of DIOS in renal carcinoma and its mechanism of action remain unclear. Objective: The purpose of this study is to investigate the effect of DIOS on cell viability and apoptosis in renal carcinoma cells and explore the possible mechanism of action. Methods: Cell viability, cytotoxicity, caspase activity, apoptosis, and expression of apoptotic related proteins were analyzed in renal carcinoma ACHN cells. Results: The results showed that DIOS inhibited the cell viability, and induced cytotoxicity and apoptosis in ACHN cells. Furthermore, DIOS increased expression of p53 mRNA and proteins, and downregulated phosphorylation of the phosphoinositide 3-kinase and protein B kinase (PI3K/AKT). In addition, it was observed that the anticancer effect of DIOS was significantly enhanced by the p53 activator, but inhibited by the p53 inhibitor. Conclusion: Our data suggested that DIOS induced apoptosis in renal carcinoma ACHN cells by reducing AKT phosphorylation through p53 upregulation.