Two Phenolic Compounds (Biscoumarin and Biflavonoid) From Ormocarpum kirkii S. Moore (Fabaceae) Exhibit Anticancer Properties Against Human Prostate Cancer Cells

Introduction: Prostate cancer (PC) is a significant global health challenge in both developed and developing nations. To contribute to the development of new and safe anticancer agents, the isolates (1-14) from Ormocarpum kirkii were investigated on human PC cells.Methods: Cell growth was determined based on the MTT assay. Cell cycle and cell death mechanisms were analysed through flow cytometry while western blotting helped to express some apoptosis and cell cycle regulatory proteins. In addition, cell migration, cell invasion, cell adhesion, and chemotaxis were assayed for the antimetastatic potential of isolates.Results: Extract (IC50: 190, 180, and 178 mu g/ml) and compounds 6 (IC50: 40, 35, and 38 mu g/ml) and 12 (IC50: 40, 36, and 32 mu g/ml) reduced DU145, PC3, and LNCaP cell survival. Compounds 6 and 12 inhibited cell proliferation and colony formation at 5 and 20 mu g/ml. They increased the number of apoptotic cells and cells in the S and G2/M phases in DU145 cells. Both compounds inhibited the number of DU145 cells invading through the matrigel membrane. Only compound 12 at 20 mu g/ml significantly (P < 0.05) abrogated the DU145 cell migration and increased cell adhesion for collagen as well as the expression of integrin beta-1 while it decreased integrin beta-4 expression. Compound 12 downregulated cdk1, pcdk1, cdk2, cyclin A, Bcl-2, N-cad, p-AKT, vimentin, and p-Rictor and upregulated Bax, p53, caspase-3, and E-cad proteins.Conclusions: Compounds 6 and 12 from O kirkii have in vitro anticancer activity through the intrinsic pathway of apoptosis and invasion inhibition.