Signaling Pathways Mediating the Cytotoxicity of (E)-4-(1-Epoxy-7,8-propenyl)phenyl Benzoate, a Phenylpropanoid from Croton velutinus , in MCF-7 Cells

Abstract

Natural products represent an important source of candidates for breast cancer therapy. Here, we investigated the antitumor activity of (E)-4-(1-epoxy-7,8-propen)phenylbenzoate (CV2), a phenylpropanoid isolated from Croton velutinus roots, in MCF-7 breast cancer cells and evaluated its toxicity profile in nontumor cells and zebrafish embryos. CV2 exhibited potent cytotoxic activity against MCF-7 cells (IC50= 4.63 ± 0.16 μM) and showed selectivity relative to nontumorigenic MCF-10A cells (SI = 9.69). CV2 also induced apoptosis, increased intracellular ROS levels, and modulated MAPK, NF-κB, and PKB/AKT signaling pathways. Pretreatment with N-acetylcysteine or MAPK inhibitors significantly attenuated CV2-induced cytotoxicity, supporting the involvement of oxidative stress and MAPK signaling in its biological effects. In toxicity studies, CV2 exhibited cytotoxicity toward peripheral blood mononuclear cells (PBMCs; IC50 = 1.75 ± 0.06 μM) and an LC50 of 3.07 μM in zebrafish embryos, accompanied by alterations in oxidative stress-related enzymes. Collectively, these findings demonstrate that CV2 possesses significant antitumor activity against breast cancer cells while highlighting the need for further studies to better define its safety profile and therapeutic potential.