Unveiling the antibreast cancer mechanism of Euphorbia hirta ethanol extract: computational and experimental study

Abstract

Breast cancer, the most prevalent cancer in women globally, is characterized by a low survival rate. Euphorbia hirta is predicted to exhibit promising antibreast cancer properties. This study aimed to explore the active compounds present in the ethanol extract of E. hirta and elucidate their mechanism for countering breast cancer using computational and experimental methodologies. The active components of the E. hirta ethanol extract were determined using Liquid chromatography high-resolution mass spectrometry. Furthermore, the identified active compounds were subjected to computational analysis involving drug-likeness screening, membrane permeability, bioactivity, toxicity assessment and protein target prediction using QSAR principles followed by molecular docking and molecular dynamics simulations. In vitro experimental investigations included toxicity, rhodamine, apoptosis, cell migration and colony formation assays. These findings indicated that six compounds with drug-like properties and physicochemical features exhibited bioactivity relevant to breast cancer. These compounds, namely, quercetin, luteolin, gallic acid, gentisic acid, quinic acid and caffeic acid, target proteins associated with breast cancer progression, including EGFR, KDR, SRC, FASN, CDK4 and ERBB2. According to molecular docking and dynamics studies, these active compounds bind securely, potentially inhibiting their target protein activity. The ethanol extract of E. hirta was toxic and selective for T47D cells. The extract induced apoptosis and loss of mitochondrial membrane potential in T47D cells, restraining their migration and colony formation. The research findings demonstrate that the extract of E. hirta effectively antagonizes breast cancer by inducing apoptosis, suppressing cellular migration, and inhibiting cell colony formation through the targeted modulation of associated proteins.