Resveratrol Triggers p53-Independent Mitochondrial Apoptosis in Castration-Resistant Prostate Cancer Cells

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Objective: Resveratrol is a pleiotropic phytochemical with reported anticancer activity, yet its mechanism in castration-resistant prostate cancer (CRPC) remains uncertain. We investigated whether resveratrol triggers a p53-independent, reactive oxygen species (ROS)-driven, mitochondria-initiated apoptotic program in DU145 cells. Methods: DU145 human prostate cancer cells were exposed to resveratrol for 24 hours. Cell viability was assessed by MTT. Apoptosis was quantified by Annexin V–FITC and propidium iodide flow cytometry. Intracellular ROS were measured using carboxy-H₂DCFDA. Mitochondrial membrane potential was evaluated with JC-1. Protein changes were analyzed by Western blot for PARP-1, NF-κB p50, and p53. Statistics used unpaired two-tailed t-tests or one-way ANOVA with p < .05 considered significant. Results: Resveratrol reduced viability in a concentration-dependent manner. Two hundred micromolar resveratrol decreased viability to approximately 56 percent of control. Following treatment, apoptotic cells significantly increased, whereas the viable fraction decreased. Intracellular ROS levels increased compared with control. JC-1 staining demonstrated pronounced mitochondrial membrane depolarization in treated cells relative to controls. Western blots showed a marked reduction of full-length PARP-1 with accumulation of its cleaved fragment, consistent with caspase activation. NF-κB p50 levels increased, whereas total p53 remained largely unchanged. Conclusion: These findings indicate that resveratrol induces apoptosis in CRPC cells through mitochondrial dysfunction and caspase-dependent mechanisms, associated with increased ROS and NF-κB activation but independent of p53.

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