Remarkable apoptotic pathway of Hemiscorpius lepturus scorpion venom on CT26 cell line

Area of Science:

• Biochemistry and Molecular Biology
• Cancer Research
• Pharmacology

Background:

• Scorpion venom contains bioactive molecules with potential anti-cancer properties.
• Inducing cancer cell death via apoptosis is a key therapeutic strategy.
• The anti-proliferative effects of Hemiscorpius lepturus venom on colon cancer are unexplored.

Purpose of the Study:

• To evaluate the anti-proliferative efficacy of Hemiscorpius lepturus scorpion venom on colon carcinoma cells.
• To investigate the apoptosis-inducing pathway of the venom in colon cancer.
• To assess the venom's therapeutic potential in a mice xenograft model.

Main Methods:

• Cell lines (CT26 and VERO) treated with varying venom concentrations.
• MTT assay for IC50 determination, flow cytometry for apoptosis analysis.
• RT-PCR to analyze Bax, Bcl2, Trp53, and Casp3 mRNA expression; mice xenograft model.

Main Results:

• Hemiscorpius lepturus venom exhibited significant anti-proliferative effects on CT26 cells (IC50 ≈ 120 μg/ml) with low toxicity to VERO cells (IC50 ≈ 896 μg/ml).
• Flow cytometry confirmed remarkable apoptosis induction in CT26 cells.
• Venom treatment led to significant upregulation of Bax, Casp3, and Trp53, and downregulation of Bcl2 mRNA in tumor tissues (p < 0.05), resulting in reduced tumor size.

Conclusions:

• Hemiscorpius lepturus venom demonstrates specific anti-proliferative and apoptosis-inducing effects on CT26 colon cancer cells via the Trp53/Bcl2/Casp3 pathway.
• The venom's potent cytotoxicity against colon cancer cells and low toxicity to normal cells suggest its potential as a novel therapeutic agent.
• Further research may explore its efficacy against other colon cancer types, paving the way for new colon cancer treatment strategies.