Background and Aim: Doxorubicin (also known as Adriamycin) is one of the most effective drugs used in breast cancer treatment. Recent medical research indicates that the extract of *Elaeagnus angustifolia* may be utilized in developing supplements for various human cancers, in conjunction with drug therapy. Therefore, the present study aims to investigate the cellular and molecular effects of Elaeagnus angustifolia ethanolic extract on the proliferation and apoptosis of breast cancer cells, as well as its synergistic effect with doxorubicin and the underlying molecular mechanisms. Materials and Methods: MCF7 breast cancer cells were obtained from the National Cell Bank of Iran (NCBI) affiliated with the Pasteur Institute (Tehran, Iran) and were cultured in RPMI1640 supplemented with 10% FBS. Cell proliferation and death were assessed using the MTT assay. DAPI staining was performed to visualize cell apoptosis. RNA was extracted from all treatment groups, and after preparing cDNA, the expression levels of apoptosis-associated genes (PTEN and BAX) and anti-apoptotic genes (BCL-2 and Akt) were measured using Real-time PCR. Results: The MTT assay results indicated that the ethanolic extract of Elaeagnus angustifolia inhibited the proliferation of MCF-7 cells and induced apoptosis. Notably, significant synergistic effects with doxorubicin were observed. DAPI staining revealed qualitative changes in cancer cell apoptosis following treatment with the alcoholic extract. Additionally, Real-time PCR results demonstrated that the Elaeagnus angustifolia extract increased the expression of the PTEN and BAX genes (p=0.023) in MCF-7 breast cancer cells while significantly decreasing the expression of the BCL-2 and Akt1 genes (p=0.042). Conclusion: The findings indicate that Elaeagnus angustifolia extract activates the apoptosis pathway in MCF-7 breast cancer cells. Thus, it presents a promising new therapeutic strategy for breast cancer treatment

Breast cancer, Elaeagnus angustifolia extract, doxorubicin, apoptosis, MCF7.