Inhibition Effects of Scorpion Venom Extracts (Buthus matensii karsch) on the Growth of Human Breast Cancer MCF-7 cells

Background: To observe the inhibition effects of the Buthus matensii Karsch (BmK) scorpion venom extracts on the growth of human breastcancer MCF-7 cells, and to explore its mechanisms.Methods: Two common tumor cells (SMMC7721, MCF-7) were examined for the one which wasmore sensitivity to scorpion venom by MTT method. Cell cycle was determined by flow cytometry. Immunocytochemistry was applied to detect apoptosis-related protein Caspase-3 and Bcl-2 levels, while the expression of cell cycle-related protein Cyclin D1 was shown byWestern blotting.Results: Our data indicated that MCF-7 was the more sensitive cell line to scorpion venom. The extracts of scorpion venom could inhibit the growth and proliferation of MCF-7 cells. Furthermore, the extract of scorpion venom induced apoptosis through Caspase-3 up-regulation while Bcl-2 down-regulation in MCF-7 cells. In addition, the extracts of scorpion venom blocked the cells from G0/G1 phase to S phase and decreased cell cycle-related protein Cyclin D1 level after drug intervention compared with the negative control group.Conclusions: These results showed that the BmK scorpion venom extracts could inhibit the growth of MCF-7 cells by inducing apoptosis and blocking cell cycle in G0/G1 phase. The BmK scorpion venom extracts will be very valuable for the treatment of breast cancer.Key words: Apoptosis, Buthus matensii Karsch, cell cycle, MCF-7, scorpion venomAbbreviations: SVE: Scorpion venom extracts ; FBS: Fetal bovine serum; MTT: 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide;BmK ; Buthus matensii Karsch; PBS: Phosphate buffered saline; PI: Propidium iodide; FCM: Flow cytometry; SDS-PAGE: Sodium dodecylsulfate polyacrylamide gel electrophoresis; DAB: Diaminobenzidine; B-NHL: B-cell non-Hodgkin's tumors; DED: Death effector domain ; PTP:Permeability transition pores ; CKIs: Cyclin-dependent kinases inhabitors; pRB: Retinoblastoma tumor suppressor protein ; CDK: Cyclin-dependent kinase