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 μg/ml) and compounds 6 (IC₅₀: 40, 35, and 38 μg/ml) and 12 (IC₅₀: 40, 36, and 32 μg/ml) reduced DU145, PC3, and LNCaP cell survival. Compounds 6 and 12 inhibited cell proliferation and colony formation at 5 and 20 µg/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 μg/ml significantly (P < 0.05) abrogated the DU145 cell migration and increased cell adhesion for collagen as well as the expression of integrin β-1 while it decreased integrin β-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.