Potential mechanisms by which oleanic and maslinic acids from Cola lateritia K. Schum (Sterculiaceae) twigs inhibit prostate cancer cell growth

Abstract

Prostate cancer (PC) therapy is fraught with various limitations, underscoring the urgency for new therapeutic approaches. Cola lateritia K. Schum is a medicinal plant traditionally used against prostate ailments. This finding aimed to assess Cola lateritia isolates’ cytotoxic potential and investigate their potential underlying mechanisms. Through column chromatography, the C. lateritia twigs dichloromethane-methanol extract of was fractionated, yielding eleven known compounds. The later were subsequently tested in cell growth, cell proliferation and/or cell migration/invasion. Among these, compounds (3) and (4) exhibited substantial, concentration-driven inhibition of cell growth [DU145 (CC₅₀ of 25 and 22 µg/ml), PC3 (CC₅₀ of 22 and 21 µg/ml), and LNCaP (CC₅₀ of 17 and 18 µg/ml), respectively], cell proliferation (DU145 cells), and the formation of cell clones (DU145 cells). These compounds also induced an increased proportion of apoptotic cells at 2.5 and 10 µg/ml in DU145 (∼25%) and LNCaP (∼35%) cells, as well as an increment in the G0/G1 phase arrested cells versus control. Both compounds (3) and (4) demonstrated an anti-migratory effect, decreased collagen and fibronectin cell adhesion. Compound (3) down-regulated proteins such as cdk1, cdk2, pcdk2, cyclin A, Bcl-2, and vimentin, while concurrently up-regulating p19, p27, p53, Bax, caspase-3, and E-cad proteins. Additionally, it elevated β-1 and β-4 integrins at 2.5 and 10 µg/ml concentrations. The anticancer potential of Cola lateritia is attributed to oleanic acid (3) and maslinic acid (4), which exhibit the potential to impede cell growth by initiating the intrinsic apoptosis pathway and exert an anti-migratory impact.