Cervical cancer is the fourth most common cancer among women, with resistance to therapy often linked to Bcl-2 overexpression. This study evaluated the anticancer activity of durian peel extract (Durio zibethinus Murray) against HeLa cells through Bcl-2-mediated apoptosis and investigated apigenin and luteolin interactions with Bcl-2 via molecular docking. The extract was prepared by ethanol maceration, characterized by phytochemical screening and GC-MS, and tested for cytotoxicity using the MTT assay, while apoptosis was assessed through Bcl-2 immunofluorescence. Phytochemical screening confirmed flavonoids, alkaloids, saponins, tannins, and triterpenoids, with GC-MS identifying over 93 bioactive compounds. The extract exhibited significant cytotoxicity with an IC₅₀ of 5.92 μg/mL, and cell viability decreased concentration-dependently (p < 0.05), accompanied by apoptotic morphological changes and reduced Bcl-2 expression. Molecular docking revealed favorable binding of apigenin and luteolin to Bcl-2, with binding energies of −6.01 and −5.55 kcal/mol, respectively. In conclusion, durian peel extract demonstrates promising anticancer activity against HeLa cells by inducing apoptosis through Bcl-2 suppression, with apigenin and luteolin serving as potential natural candidates for cervical cancer therapy.
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