Remarkable apoptotic pathway of Hemiscorpius lepturus scorpion venom on CT26 cell line
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Scorpion venom, considered as a treasure trove of various bioactive molecules, is a new approach to induce cancer cell death via apoptosis pathways. In the present study, we evaluated for first time the anti-proliferative efficacy of Hemiscorpius lepturus scorpion venom and its pathway on a colon carcinoma cell.
Materials and methods
The CT26 and VERO cell lines were treated with various concentrations of the venom. The IC50 values were estimated by MTT assay test, and the apoptosis was evaluated by flow cytometry. Moreover, RT-PCR analysis was used to investigate the levels of Bax, Bcl2, Trp53, and Casp3 mRNA expression. The mice xenograft model was established to evaluate the therapy efficiency of venom. Some valuable exponential growth parameters were evaluated in treated mice.
The scorpion venom inhibited the growth of CT26 cells with an IC50 value about 120 μg/ml. However, VERO cells increased to 896 μg/ml under the same condition. A remarkable apoptotic cells in CT26 cells were revealed by flow cytometry assay. A significant over-expression was observed in Bax, Casp3, and Trp53 and downregulated in Bcl2 mRNA level in tumor tissue after treatment with scorpion venom (p < 0.05). All changes of valuable exponential growth parameters showed a shrinking tumor size.
Our findings indicated that Hemiscorpius lepturus venom has a special anti-proliferative effect on CT26 cells via Trp53/Bcl2/Casp3 pathway. Considering its powerful cytotoxic vigor against a colon cancer cell (CT26) and low toxicity to non-tumorigenic cell (VERO), we propose that this venom probably has a specific effect on other colon cancer cells and may turn out to be a novel therapeutic strategy in treating colon cancer.
KeywordsScorpion venoms Apoptosis Neoplasms Hemiscorpius lepturus Colorectal cancer Antineoplastic natural compounds
This study was financially supported by the Hamadan University of Medical Sciences. The study was funded by the Research Center for Molecular Medicine, Hamadan University of Medical Sciences (No. 9412257461).
Compliance with ethical standards
The animal studies were performed in accordance with the experimental protocols of the animal ethics committee of Hamadan University of Medical Sciences (No. 9412257461).
All applicable international, national, and institutional guidelines for the care and use of animals were followed.
For this type of study, formal consent is not required.
Conflict of interest
The authors declare that they have no conflicts of interest.
- Al-Asmari AK, Riyasdeen A, Islam M. Scorpion venom causes upregulation of p53 and downregulation of Bcl-x(L) and BID protein expression by modulating signaling proteins Erk(1/2) and STAT3, and DNA damage in breast and colorectal Cancer cell lines. Integr Cancer Ther. 2017;17:271–81.CrossRefGoogle Scholar
- Diaz-Garcia A, Morier-Diaz L, Frion-Herrera Y, Rodriguez-Sanchez H, Caballero-Lorenzo Y, Mendoza-Llanes D, et al. In vitro anticancer effect of venom from Cuban scorpion Rhopalurus junceus against a panel of human cancer cell lines. J Venom Res. 2013;4:5–12.Google Scholar
- Du Q, Hou X, Ge L, Li R, Zhou M, Wang H, et al. Cationicity-enhanced analogues of the antimicrobial peptides, AcrAP1 and AcrAP2, from the venom of the scorpion, Androctonus crassicauda, display potent growth modulation effects on human cancer cell lines. Int J Biol Sci. 2014;10:1097–107.CrossRefGoogle Scholar
- Li B, Lyu P, Xi X, Ge L, Mahadevappa R, Shaw C, Kwok HF. Triggering of cancer cell cycle arrest by a novel scorpion venom-derived peptide-Gonearrestide. 2018;22:4460–4473.Google Scholar
- Mehrara E. Quantitative analysis of tumor growth and response to therapy, Department of Physics, Institutionen för fysik. 2010Google Scholar
- Moradi M, Solgi R, Vazirianzadeh B, Tanzadehpanah H, Saidijam M. Scorpion venom and its components as new pharmaceutical approach to cancer treatment, a systematic review. Int J Pharm Sci Res. 2018b;9:1000–12.Google Scholar
- Wang Z-P, Zhang W-D, Zhang J, Jia Q, Song S-Q, Wang Z-X, et al. Inhibition of polypeptide extract from scorpion venom (PESV) against proliferation of prostate cancer androgen-independent cell lines in vitro. Chin Pharmacol Bulltin. 2006;22:938.Google Scholar
- Zhang W, Zhang Y, Wang Z, Wang Z, Jia Q. Effect of polypeptide extract from scorpion venom on tumor growth and cellular immunity in rats with W256 sarcocarcinoma. J Shandong Univ. 2007;3:018.Google Scholar