ANTIPROLIFERATIVE AND APOPTOSIS-INDUCING EFFECTS OF JUGLANS REGIA L. LEAF EXTRACT ON HUMAN BREAST ADENOCARCINOMA (MCF-7) CELLS
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Background (Relevance): Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancer-related death in women worldwide. The limitations of conventional therapies, including severe side effects and drug resistance, necessitate the exploration of novel therapeutic agents, particularly from natural sources. Juglans regia (walnut) leaves are known in traditional medicine for their astringent, antioxidant, and anti-inflammatory properties, attributed to a high content of phenolic compounds, flavonoids, and naphthoquinones like juglone. However, their specific cytotoxic mechanisms against breast cancer cells are not comprehensively understood. Objective: This study aimed to investigate the in vitro antiproliferative activity and the apoptosis-inducing potential of an ethanolic extract of Juglans regia leaves (JRLE) on the human breast cancer cell line MCF-7. Methods: Juglans regia leaves were collected from the Andijan region, Uzbekistan, identified, and subjected to ethanolic extraction. MCF-7 cells were cultured and treated with various concentrations of JRLE (0-600 µg/mL) for 24, 48, and 72 hours. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The induction of apoptosis was analyzed by Annexin V-FITC/Propidium Iodide (PI) double staining using flow cytometry. Results: JRLE demonstrated a significant dose- and time-dependent cytotoxic effect on MCF-7 cells. The half-maximal inhibitory concentration (IC₅₀) value was found to be 210.8 ± 14.5 µg/mL after 48 hours of exposure. Flow cytometry analysis confirmed that JRLE induced apoptosis. Treatment with JRLE (at 210 µg/mL and 420 µg/mL) for 48 hours led to a significant increase in the percentage of cells in the early and late apoptotic stages, totaling 31.4% and 58.2% respectively, compared to 5.1% in the untreated control group. Conclusion: The findings suggest that the ethanolic extract of Juglans regia leaves possesses potent anticancer properties by inhibiting MCF-7 cell proliferation and inducing programmed cell death via apoptosis. JRLE warrants further investigation as a potential source for the development of novel phytotherapeutic agents for breast cancer.
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