Gallic Acid Potentiates Cisplatin Response in Cervical Cancer Cells Through Coordinated Cellular and Molecular Alterations

Cisplatin (Cis) resistance and dose-limiting toxicity remain major challenges in the treatment of cervical cancer, necessitating the development of more effective combination strategies. The effects of gallic acid (GA), alone and in combination with Cis, were evaluated in HeLa cervical cancer cells using cell viability, apoptosis, gene expression, caspase activity, and cytokine profiling assays. Drug interactions were assessed using the Chou–Talalay method. The GA+Cis combination was associated with enhanced cytotoxicity compared to single-agent treatments, with combination index (CI) values ranging from 0.61 to 0.92, indicating synergistic interactions. Selectivity index (SI) values exceeding 2 at 48 h suggested preferential cytotoxicity toward cancer cells. The combination treatment significantly increased apoptotic cell populations and was accompanied by elevated caspase-3 and caspase-9 activities. Gene expression analysis revealed increased BAX and CASP3 levels, along with decreased BCL2 and BIRC5 expression, resulting in an increased BAX/BCL2 ratio. In addition, cell cycle analysis indicated accumulation in the G2/M phase, while cytokine profiling demonstrated reduced levels of pro-inflammatory cytokines and increased IL-10 levels under combination treatment conditions. These findings suggest that GA enhances the biological activity of Cis in cervical cancer cells through coordinated modulation of apoptosis, cell cycle dynamics, and inflammatory signaling. However, these results are based on in vitro observations, and further in vivo and mechanistic studies are required to confirm the therapeutic potential of this combination strategy.