Rhopalurus junceus scorpion venom induces antitumor effect in vitro and in vivo against a murine mammary adenocarcinoma model

Alexis Diaz Garcia

LIFESCOZUL CHILE SpA

Jenny Laura Ruiz-Fuentes

Pedro Kourí Tropical Medicine Institute

Yahima FRION Herrera

Università Ca' Foscari Venezia

Arianna Yglesias

LABIOFAM

Yanelis Riquenes Garlobo

LABIOFAM Entrepreneurial Group, Cuba, Havana

Hermis Rodríguez Sánchez

Pedro Kourí Tropical Medicine Institute

Juan C Rodríguez Aurrecochea

Ledys X Lopez Fuentes

Resumen

Objectives: In Cuba the endemic scorpion species Rhopalurus junceus has been used in traditional medicine for cancer treatment and related diseases. However there is no scientific evidence about its therapeutic potential for cancer treatment. The aim of the study was to determine the antitumor effect of scorpion venom against a murine mammary adenocarcinoma F3II. Materials and methods: The cytotoxic activity was determined by MTT assay with venom concentrations ranging from 0.1-1 mg/ml. Apoptosis was determined by RT-PCR and flow cytometry. Toxic effect in healthy animals and tumor growth kinetics in F3II bearing-mice were evaluated by using scorpion venom doses (0.2; 0.8; 3.2 mg/kg) after one and ten injections respectively by the intraperitoneal route . Results: Scorpion venom induced a significant cytotoxic effect (P<0.05) in F3II cells in a concentration-dependent manner. The cell death event involves the apoptotic pathway due to up-regulation of pro-apoptotic genes (p53, bax), down-regulation of antiapoptotic gene (bcl-2), and 33% of Annexin V+/PI- cells at early apoptosis and 10.21% of Annexin V+/PI+ cells at late apoptosis. Scorpion venom induced significant inhibition of tumor progression (P<0.05) in F3II bearing-mice in a dose-dependent manner. The antitumor effect was confirmed due to dose-dependent reduction of Ki-67 and CD31 proteins present in tumor tissue. Conclusion: Evidence indicates that scorpion venom can be an attractive natural product for deep investigation and developing a novel therapeutic agent for breast cancer treatment.