Antitumor and antiproliferative potential of crotoxin in triple negative breast tumors

Triple negative breast carcinoma represents around 15 % of breast cancer cases. Is a type of breast cancer with poor prognosis, because it has a high rate of recurrence, metastasis and death and can be resistant to therapy. The recommended treatment is the use of anthracyclines with taxanes, however, these medications have several side effects. Thus, there is a need for new therapeutic approaches. Crotoxin, the main toxin found in the venom of the South American rattlesnake Crotalus durissus terrificus, is a potent β-neurotoxin that has phospholipase A2 (PLA2) activity. It exhibits preferential cytotoxic activity against several types of tumor cells and is most cytotoxic to cell lines that express high levels of epidermal growth factor receptors. Considering this, in this study, we evaluated the biological mechanisms that trigger the antitumor effects of crotoxin in a cell line representing triple negative breast carcinoma (MDA-MB-231 tumor cells). Results demonstrated that crotoxin had anti-apoptotic, anti-autophagic and pro-necrotic actions. The pro-necrotic effect occurred through mechanisms of apoptosis evasion, autophagy inhibition and DNA damage. Therefore, this study represents an important milestone to better understand the effects and mechanisms of action of crotoxin in triple negative breast cancer.