Ferula orientalis Extract Induces Mitochondrial Apoptosis Through Redox Modulation in MDA-MB-231 Triple-Negative Breast Cancer Cells

Objective: Triple-negative breast cancer (TNBC) is an aggressive molecular subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. Due to limited targeted therapeutic options and intrinsic redox adaptations, TNBC cells exhibit increased oxidative vulnerability, making redox modulation a promising therapeutic strategy. Ferula orientalis, a phytochemically rich medicinal plant, has been reported to possess bioactive compounds with potential anticancer properties. However, its effects on redox homeostasis and mitochondrial apoptosis in TNBC cells remain largely unexplored. This study aimed to investigate the impact of Ferula orientalis extract on oxidative stress parameters, antioxidant enzyme activities, and apoptosis-related gene expression in the MDA-MB-231 TNBC cell line.Materials and Methods: MDA-MB-231 cells were treated with F. orientalis extract at concentrations of 10, 50, and 100 µg/mL for 24 hours. Intracellular reduced glutathione (GSH) and malondialdehyde (MDA) levels were measured spectrophotometrically to assess redox status. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities were determined using enzymatic assays. Apoptosis-related gene expression levels (Bax and Bcl-2) were quantified by RT-qPCR using the 2^−ΔΔCt method. Statistical analyses were performed using one-way ANOVA followed by Tukey’s post hoc test.Results: Treatment with F. orientalis resulted in a dose-dependent depletion of GSH and a significant elevation of MDA levels, indicating enhanced oxidative stress. Antioxidant enzyme activities (SOD, CAT, and GPX) were significantly suppressed across treatment groups. Furthermore, Bax expression was upregulated, whereas Bcl-2 expression was downregulated, leading to a marked increase in the Bax / Bcl-2 ratio. These findings collectively demonstrate activation of mitochondrial apoptotic signaling in response to extract-induced redox imbalance.Conclusion: Ferula orientalis extract disrupts redox homeostasis and promotes oxidative stress–mediated mitochondrial apoptosis in TNBC cells. The dual mechanism involving enhancement of oxidative burden and suppression of anti-apoptotic defenses highlights the potential of F. orientalis as a redox-targeted complementary therapeutic candidate in TNBC. Further studies are required to identify active constituents and validate these findings in in vivo models.