A Functional Evaluation of Resveratrol–Paclitaxel Combination Reveals Enhanced Apoptotic Responses in HeLa Cells

This study evaluated the combined effects of resveratrol (RES) and paclitaxel (PAC) on cell viability, apoptotic responses, and associated cellular processes in HeLa cervical cancer cells. Antiproliferative activity was assessed using XTT assay and combination index (CI) analysis, while apoptosis, cell cycle distribution, mitochondrial membrane potential (ΔΨm), and intracellular reactive oxygen species (ROS) levels were examined by flow cytometry-based approaches. The RES + PAC combination produced a synergistic reduction in cell viability compared to single treatments. This effect was accompanied by increased apoptotic cell populations and a marked accumulation of cells in the G2/M phase. Combined treatment was also associated with a pronounced loss of mitochondrial membrane potential and elevated ROS levels. Gene expression analysis indicated an increased Bax/Bcl-2 mRNA ratio together with upregulation of apoptosis-related markers and downregulation of cell cycle regulators. Importantly, pharmacological inhibition of ROS using N-acetylcysteine (NAC) partially attenuated both ROS accumulation and the reduction in cell viability, suggesting that oxidative stress contributes, but is not solely responsible, for the observed cytotoxic effects. Overall, these findings indicate that the combination of RES and PAC enhances apoptotic responses in HeLa cells through mechanisms associated with mitochondrial dysfunction, oxidative stress, and cell cycle perturbation. Further studies are required to clarify the underlying pathways and to evaluate the translational relevance of these findings.