2-Benzoxazolinone as Breast Cancer Cells Inhibitor via Estrogen Receptor

Abstract

Estrogen receptors alpha (ERα) and beta (ERβ) is highly expressed in different cancer cells. Inhibition of ERs by small molecules is a promising approach to developing novel anticancer agents amidst increased endocrine therapy resistance. A heterocyclic molecule, 2-benzoxazolinone (2-BOA) and its derivatives, found in Acanthus ilicifolius leaves, possesses anticancer on varied cancer cell types such as HeLa, MCF-7, A-549, and SW-480. However, the mechanism of its cancer cell growth inhibition is an enigma. This study aimed to unmask the activity of 2-BOA to inhibit the growth of the MCF-7 breast cancer cell line via estrogen receptors. The modulation mechanism was predicted by docking molecular of 2-BOA toward ERα (PDB ID: 2JF9) and ERβ (PDB ID: 5TOA). Subsequently, the MCF-7 cell viability assay was performed to validate the in-silico prediction. We preliminary identified the presence of 2-BOA in Acanthus ilicifolius leaves using high-performance liquid chromatography (HPLC). The binding energy of 2-BOA on ERα and ERβ exhibited a similar score (-6.3 kcal/mol). 2-BOA showed inhibition toward the MCF-7 breast cancer cell line with IC50 value 35.4 µM. 2-BOA may be a potent small molecule inhibitor of the MCF-7 breast cancer cell growth via estrogen receptors.