Estrogen receptor-positive (ER+)
breast cancer is the most diagnosed subtype of
breast cancer. Currently,
aromatase inhibitors (AIs) are used as first-line treatment option in this type of
tumors, however they cause several side effects, which is why new therapeutic approaches are demanding. The South American rattlesnake Crotalus durissus terrificus produces a
venom enriched in several bioactive substances, like
phospholipases A2 (PLA2). One of those is
crotoxin, a β-
neurotoxin, that has already been reported for its anti-
cancer properties in different
cancers. Recently, its clinical interest has emerged and, in fact, a clinical trial in patients with advanced
cancer is underway. Considering this, in this work, we studied the biological mechanisms behind the anti-
cancer effects of
crotoxin B (CTX) in an ER+
aromatase-overexpressing
breast cancer cell line (MCF-7aro cells). Results revealed that CTX impairs MCF-7aro cells growth, through a cell cycle arrest at G2/M phase, inhibition of ERK1/2 pathway and by apoptosis through activation of
caspase-8. In addition, it can be considered a safe natural compound as did not affect non-cancerous cells and only showed anti-growth effects in
breast cancer cells. Therefore, this study represents an important landmark to better understand the effects and mechanisms of action of
crotoxin in ER+
breast cancer.