Exploring the therapeutic potential of scorpion venom to mitigate colorectal cancer biomarkers in rats

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. The limitations of conventional therapies, namely severe side effects and the emergence of drug resistance, underscore the urgent need for novel and more effective treatment strategies. Natural products, including bioactive compounds derived from scorpion venom (SV), have demonstrated promising anticancer properties in various studies. This study aimed to investigate the potential chemopreventive and therapeutic effects of Leiurus quinquestriatus venom (LQV) and Androctonus bicolor venom (ABV) against chemically induced CRC in a rat model. Male rats were randomly assigned to four groups: Group 1 (Gp1) (control), Gp2 (CRC induced using 40 mg/kg 1,2-dimethylhydrazine (DMH), administered subcutaneously for 4 weeks), and Gp3 and 4 (DMH-induced CRC treated intraperitoneally with 0.025 mg/kg LQV and 0.05 mg/kg ABV, respectively, for 11 weeks). At the end of the experimental period, colon tissues were collected for histopathological examination, tumor biomarker analysis, gene expression profiling, cell cycle distribution, and apoptotic assays. Both LQV and ABV significantly reduced the number of aberrant crypt foci (ACF) and mucin-depleted foci (MDF) while enhancing the number of goblet cells in colonic mucosa. Treatment also resulted in a marked downregulation of proliferating cell nuclear antigen (PCNA) and cyclin D1 and upregulation of the tumor suppressor gene PTEN. Moreover, flow cytometry analysis revealed an increase in late apoptotic cells and cell cycle arrest at sub-G1 and G0 phases in venom-treated groups. These findings suggest that LQV and ABV possess notable anti-CRC activity through modulation of proliferation, apoptosis, and gene regulation, highlighting their potential as candidates for alternative CRC therapies.