Cisplatin and ε-Viniferin Synergistically Modulate Oxidative Stress in HeLa Cells: Implications for Redox Modulation in Cervical Cancer Cells

This study investigates the combined effects of cisplatin (CDDP) and ε-viniferin (ε-VNF), a natural stilbenoid, on oxidative stress and apoptosis in HeLa cells. Cytotoxicity was assessed using the MTT assay, and IC50 values were determined as 28 µM for CDDP and 21 µM for ε-VNF. Synergistic and antagonistic combination ratios of these doses were tested. Oxidative stress was evaluated via Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Oxidative Stress Index (OSI), Superoxide Dismutase (SOD), Reduced Glutathione (GSH), and Malondialdehyde (MDA). Apoptosis was measured using Annexin V-FITC/PI staining and caspase-9 activation assays. TAS levels significantly increased in all combination groups compared to the control (control: 266.7 ± 0.1 µmol/L; 20% combo: 2466.7 ± 1.0 µmol/L). OSI values decreased accordingly (control: 22.5 ± 7.1; 10% combo: 1.6 ± 0.5). GSH levels decreased in the combination groups (e.g., 20%: 0.8 ± 0.2 µM vs. control: 1.4 ± 0.1 µM), while MDA levels increased (20%: 3.8 ± 0.5 µM vs. control: 0.5 ± 0.1 µM). Caspase-9 positive cells increased markedly (20%: 55.0% vs. control: 13.2%), supporting activation of the mitochondrial apoptotic pathway. Annexin V analysis revealed increased late apoptosis (20%: 76.1%) and early apoptosis (20%: 17.0%).