Breast cancer is the most common malignancy accounting for 38.8% of all malignancies among Egyptian women. This study aimed to investigate the A. muricata leaves extract and its active fraction in inhibiting cell proliferation in the human MDA-MB-231 cell line as a model of Triple Negative Breast Cancer. MDA-MB-231 cell lines were seeded and maintained in RPMI 1640 culture medium. RNAs were isolated from non-treated MDA-MB-231 and treated cell lines with A. muricata DMSO extract after 72 hrs incubation using TriPure isolation reagent. qRT-PCR was applied to measure the gene expression of P₅₃, and Bcl₂ against the β-actin gene as an internal control. Protein analysis of BRCA₁, BRCA₂, EGFR, p53, Bcl2, Cytochrome C, and Caspase3 gene expression was carried out by ELIZA immunoassay. The level of expression of the pro-apoptotic P₅₃ gene in the treated cell line with A. muricata DMSO extract was overexpressed, indicating its potential efficacy in directing cancer cells toward programmed death. On the other hand, the treated cell line significantly (P = 0.05) showed low expression of BRCA₁, BRCA₂, and EGFR when compared to the negative control. The present study revealed that A. muricata leaves extract is a promising inhibitor of cell proliferation in the MDA-MB-231 cell line (TNBC), and has efficacy against BRCA₁, BRCA₂, and EGFR gene expression. Since this plant is widely consumed by humans and is non-toxic, it could be developed quickly for chemoprevention and intervention in breast cancer patients.