Synergism between Rhopalurus junceus venom and cytostatics in HeLa

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J Pharm Pharmacogn Res 7(1): 67-76, 2019. DOI: https://doi.org/10.56499/jppres18.433_7.1.67 Original Article Synergistic effect of Rhopalurus junceus scorpion venom combined with conventional cytostatics in cervical cancer cell line HeLa [Efecto sinérgico de la combinación del veneno de escorpión Rhopalurus junceus con citostáticos convencionales en la línea celular tumoral HeLa] Arianna Yglesias-Rivera1, Hermis Rodríguez-Sánchez2, Alexis Díaz-García1* 1Research Department, Laboratories … Continue reading Synergism between Rhopalurus junceus venom and cytostatics in HeLa

J Pharm Pharmacogn Res 7(1): 67-76, 2019.

DOI: https://doi.org/10.56499/jppres18.433_7.1.67

Original Article

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

[Efecto sinérgico de la combinación del veneno de escorpión Rhopalurus junceus con citostáticos convencionales en la línea celular tumoral HeLa]

Arianna Yglesias-Rivera1, Hermis Rodríguez-Sánchez2, Alexis Díaz-García1*

1Research Department, Laboratories of Biopharmaceuticals and Chemistries Productions (LABIOFAM), Havana, Cuba.
2Microbiology Department, Tropical Medicine Institute “Pedro Kouri”, Havana, Cuba.

*E-mail: alediaz@ipk.sld.cu

Abstract

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.

Keywords: chemotherapy drugs; cytotoxicity; HeLa; Rhopalurus junceus scorpion venom; synergism.

Resumen

Contexto: El veneno del escorpión endémico de Cuba Rhopalurus junceus disminuye la viabilidad de células tumorales epiteliales y no afecta las células normales. La quimioterapia convencional induce efecto citotóxico no específico sobre las células tumorales y normales. Las interacciones farmacológicas del veneno de escorpión con citostáticos convencionales no han sido estudiadas.

Objetivos: Evaluar el efecto citotóxico de los citostáticos, solos y combinados con el veneno de escorpión Rhopalurus junceus, en las células tumorales y normales, HeLa y Vero, respectivamente.

Métodos: Las células se trataron con los citostáticos solos a diferentes concentraciones de 5-fluorouracilo (0,5; 5; 50; 500 y 5000 µM), doxorrubicina (0,005; 0,05; 0,5; 5 y 50 µM) y cisplatino (3,13; 6,25; 12,5; 25 y 50 µM) y combinados con la ½ CI50 (0,5 mg/mL) en HeLa del veneno de escorpión. La viabilidad celular se determinó mediante el ensayo de MTT. El índice de combinación e índice de reducción de la dosis, se determinaron mediante el software CompuSyn.

Resultados: El tratamiento combinado del veneno de escorpión con 5-fluorouracilo, cisplatino y doxorrubicina a 0,5 - 500 µM, 3,13 - 25 µM y 0,005 - 5 µM, respectivamente, ejerció un efecto sinérgico sobre la citotoxicidad de HeLa. Mientras que la mayor concentración de los citostáticos, combinado con el veneno indujo efectos antagónicos. En células Vero no se obtuvieron diferencias significativas, entre el efecto citotóxico del tratamiento individual de los citostáticos 5-fluorouracilo, cisplatino y doxorrubicina o combinados con el veneno, respectivamente.

Conclusiones: El veneno de escorpión Rhopalurus junceus potencia selectivamente la citotoxicidad a bajas concentraciones de los citostáticos, en la línea tumoral cérvico-uterina HeLa.

Palabras Clave: citotoxicidad; HeLa; quimioterapia; sinergismo; veneno de escorpión Rhopalurus junceus.

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Citation Format: Yglesias-Rivera A, Rodríguez-Sánchez H, Díaz-García A (2019) Synergistic effect of Rhopalurus junceus scorpion venom combined with conventional cytostatics in cervical cancer cell line HeLa. J Pharm Pharmacogn Res 7(1): 67–76. DOI: https://doi.org/10.56499/jppres18.433_7.1.67

© 2019 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

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