Synergistic effect of Rhopalurus junceus scorpion venom combined with conventional cytostatics in cervical cancer cell line HeLa

Alexis Diaz Garcia

LIFESCOZUL CHILE SpA

Arianna Yglesias

LABIOFAM

Hermis Rodríguez Sánchez

Pedro Kourí Tropical Medicine Institute

Gabino Garrido

Journal of Pharmacy & Pharmacognosy Res

Resumen

Efecto sinérgico de la combinación del veneno de escorpión Rhopalurus junceus con citostáticos convencionales en la línea celular tumoral HeLa] Abstract Resumen Context: Venom from endemic scorpion of Cuba, Rhopalurus junceus, decreases the viability of epithelial cancer cells and has negligible cytotoxic effect on normal cells. Conventional chemotherapy induces unspecific cytotoxic effect against cancer and normal cells. Pharmacological interaction of this scorpion venom with conventional cytostatics is unknown. Aims: To evaluate the cytotoxic effect of combined treatment of Rhopalurus junceus scorpion venom and conventional cytostatics in the cervical cancer and kidney normal cell line HeLa and Vero, respectively. Methods: Both cell lines were treated alone with different concentrations of 5-fluoruracil (0.5, 5, 50, 500 and 5000 µM), doxorubicin (0.005, 0.05, 0.5, 5 and 50 µM) and cisplatin (3.13, 6.25, 12.5, 25 and 50 µM) or combined with ½IC50 in HeLa (0.5 mg/mL) of scorpion venom. Cell viability was determined by MTT assay. The combination index and dose reduction index at different concentration levels were generated by CompuSyn software. Results: Rhopalurus junceus scorpion venom exerted synergic effect in HeLa cancer cell line when combined with 5-fluorouracil, cisplatin and doxorubicin at 0.5-500 µM, 3.13-25 µM and 0.005-5 µM, respectively. Meanwhile, higher concentration levels of cytostatics combined with scorpion venom induced antagonist effects. Besides, 5-fluorouracil, cisplatin and doxorubicin as single treatment and combined with scorpion venom did not showed significant differences respect to cell viability in Vero cells. Conclusions: Rhopalurus junceus scorpion venom is able to potentiate selectively the cytotoxicity, at low concentrations of chemotherapy drugs, against the cervical cancer cell line HeLa.