Heteroctenus junceus scorpion venom induces in vivo apoptosis of F3II tumor cells and increases the antineoplastic effect of cisplatin in vitro
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https://doi.org/10.15625/vjbt-24452Keywords:
Apoptosis,, Heteroctenus junceus,, scorpion venom,, synergism.Abstract
Heteroctenus junceus scorpion venom has been frequently used in traditional medicine as an anti-inflammatory, analgesic, and antitumor agent. This venom has been shown to reduce tumor volume in mice carrying a tumor induced by the F3II metastatic tumor cell line. However, the type of cell death that the venom promotes in vivo, as well as its ability to potentiate the antineoplastic effects of cytostatic agents used in clinical practice, remains unknown. To determine the ability of H. junceus scorpion venom to induce apoptosis in vivo and to evaluate the effect of combined scorpion venom and chemotherapy treatment in the F3II mouse tumor model. In vivo apoptosis was assessed by immunohistochemistry using the commercial kit ApopTag in tumors extracted from mice treated orally with H. junceus scorpion venom. In addition, F3II murine tumor cells were treated with a simultaneous combination of H. junceus scorpion venom with cisplatin or cyclophosphamide. In vitro, the combination index and dose reduction index were determined. Oral treatment with 12.5 mg/kg (p < 0.01) and 25 mg/kg (p < 0.001) of venom, compared to the negative control group (0 mg/kg of venom), induced a statistically significant increase in the number of TUNEL-positive cells. Therefore, the same doses of venom that exhibit an antitumor effect in the F3II model are capable of inducing DNA fragmentation in a ladder pattern. The combination of venom with chemotherapy in vitro synergistically increased its cytotoxicity, depending on its concentration and the type of cytostatic agent. The scorpion venom of H. junceus increases DNA fragmentation in vivo, suggesting that it may inhibit the resistance to apoptosis of tumor cells. The venom synergistically enhances the antineoplastic effect of cisplatin in the murine F3II breast tumor cell line.
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