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.

卵巢癌是第六大常见妇科恶性肿瘤。从巴勒斯坦毒蝎（Scorpio maurus palmatus）毒液中分离得到的阳离子抗菌肽Smp43，对革兰氏阳性菌、革兰氏阴性菌均具有显著的抗菌活性，同时具备抗真菌活性。本研究评估了Smp43的抗癌功效，并考察了其对人卵巢癌细胞系OVCAR-3的细胞活力、细胞周期进程、细胞凋亡、细胞坏死以及氧化应激的影响。与正常成纤维细胞系WI-38相比，Smp43可显著降低OVCAR-3细胞的活力，二者的半数抑制浓度（IC₅₀）分别为7.75 μg/mL和29.50 μg/mL。该肽可有效诱导OVCAR-3细胞发生G1期细胞周期阻滞与细胞凋亡，其通过下调促存活标志物Bcl-2，同时上调促凋亡标志物Bax、p53、半胱天冬酶-3（caspase-3）、半胱天冬酶-8（caspase-8）与半胱天冬酶-9（caspase-9），调控凋亡相关标志物的表达。此外，Smp43可显著增加OVCAR-3细胞的DNA断裂水平，并降低抗氧化相关参数。上述研究结果表明，Smp43具有潜在的抗卵巢癌活性，其作用机制涉及诱导细胞凋亡、细胞坏死、G1期细胞周期阻滞以及抑制抗氧化防御系统。