Scorpion antimicrobial peptides Smp24 and Smp43 promote caspase-dependent apoptosis in glioma U87MG and prostate PC3 cell lines <i>in vitro</i>

Background and aim Smp24 and Smp43 are cationic antimicrobial peptides from the Egyptian scorpion Scorpio maurus palmatus. Prior studies showed their cytotoxic effects on various cancer cell lines, including blood, liver, lung, and breast cancers. This study explored the mechanisms of Smp24 and Smp43 in glioma (U87MG) and prostate cancer (PC3) cells.Methods Cytotoxicity was assessed after 24-h treatment (2.5–40 µM) using CellTiter-Glo® for ATP levels and LDH assays for membrane integrity. At IC50 concentration, nuclear morphology was examined by Hoechst 33342/PI dual staining, and apoptosis by Annexin V/PI and cell cycle were analyzed by flow cytometry. Gene expression of apoptosis markers (CASP3, CASP8, CASP9, PARP1) was measured by RT-PCR. Protein activation of caspase-3 and PARP-1 was analyzed by Western blot, with caspase-3 involvement confirmed using the inhibitor Ac-DEVD-CHO.Key findings and conclusion Both peptides reduced viability and induced cytotoxicity in a dose-dependent manner, as evidenced by decreased ATP levels and increased LDH release. Morphological apoptosis features were observed with Hoechst/PI staining and confirmed by Annexin V/PI staining. In addition, PC3 cells only showed G2/M arrest. RT-PCR indicated upregulation of apoptosis markers, and Western blot confirmed caspase-3 activation and PARP-1 cleavage. Furthermore, Ac-DEVD-CHO attenuated peptide-induced cytotoxicity, supporting caspase-dependent apoptosis. Taken together, this study shows that Smp24 and Smp43 exhibit potent cytotoxicity against glioma and prostate cancer cells through caspase-dependent apoptosis, emphasizing their potential as the novel candidates for cancer therapy.