Scorpion venom cytolytic peptide Smp43 induces caspase-dependent apoptosis in ovarian carcinoma cell line OVCAR-3

Ovarian cancer ranks as the sixth most prevalent type of gynecological cancer. Smp43, a cationic antimicrobial peptide isolated from the scorpion venom of <i>Scorpio maurus palmatus</i>, exhibits notable antibacterial, against both Gram-positive and Gram-negative bacteria, and antifungal activities. This study evaluates the anti-cancer efficacy of Smp43 and examines its effects on cell viability, cell cycle progression, apoptosis, necrosis, and oxidative stress in a human ovarian cancer cell line (OVCAR-3). Smp43 significantly reduced the viability of OVCAR-3 cells compared to the normal fibroblast cell line WI-38, with IC₅₀ values of 7.75 µg/mL and 29.50 µg/mL, respectively. The peptide effectively caused G1 phase cell cycle arrest and apoptosis in OVCAR-3 cells. It modulated apoptotic markers by downregulating the pro-survival marker Bcl-2 while upregulating the pro-apoptotic markers Bax, p53, caspase-3, caspase-8, and caspase-9. Additionally, Smp43 significantly increased DNA fragmentation in OVCAR-3 cells and decreased antioxidant parameters. These findings suggest that Smp43 possesses potential anti-ovarian carcinoma properties, exerting its effects through mechanisms involving apoptosis induction, necrosis, G1 cell cycle arrest, and inhibition of the antioxidant defense system.