3-NAntC: a novel Crotoxin B-derived peptide for the treatment of triple-negative breast cancer

Abstract

Abstract Breast cancer is the most prevalent type of tumor and a major leading cause of cancer mortality. Triple-negative breast cancer (TNBC) has the worst prognosis due to its malignant characteristics and the absence of efficacious treatments. Crotoxin, a protein in Crotalus genus snake venom, has proven antitumor activity against aggressive solid tumors, but marked toxicity in humans. Crotoxin B-derived peptides were synthesized and evaluated in vitro for their antitumor activity, which resulted in the discovery of 3-NAntC. 3-NAntC (1µg/mL) treatment for 72 hours decreased the MDA-MB-231 cells viability to 49.0%±17.5% (p < 0.0001), while the same condition resulted in the viability of HMEC cells at 98.2%±13.8%. 3-NAntC exhibited higher antitumoral activity in vitro than cisplatin and similar effect of doxorubicin. 3-NAntC reduced MDA-MB-231 cell proliferation and caused a G2/M arrest. 3-NAntC primarily induced apoptosis, with a lower necrosis occurrence compared with doxorubicin. 3-NAntC caused a low LDH release, and its cytotoxicity was not impaired by the autophagy inhibitor 3-MA. In zebrafish in vivo model, 3-NAntC was very well tolerated, showing no lethal effect and a low malformation rate at ≤ 75mg/mL. 3-NAntC is a novel synthetic peptide with promising antitumor effects in vitro against TNBC cells and with low toxicity in vivo.