Chemosensitizing Effects of Resveratrol Derivatives on p53-dependent Apoptosis Triggered by Cisplatin in Human Lung Cancer Cells

Background/Aim: Although cisplatin is a standard treatment for lung cancer, its effectiveness is often limited by tumor chemoresistance and severe side effects, driving the search for approaches that can restore drug sensitivity. Resveratrol (Res) exhibits anticancer properties, but its clinical application is hindered by poor stability and low bioavailability. This study investigated the chemosensitization effect of YI-7, a Res derivative with modified pharmacophore benzyloxy substitutions that sensitized to p53-dependent apoptosis triggered by cisplatin in human lung cancer cells. Materials and Methods: The IC₅₀ of YI-7 in A549 human lung cancer cells was determined using the MTT viability assay. Cell proliferation was further examined using a colony formation assay. Chemosensitizing effects were assessed by pretreating cells with cisplatin (25 μM), followed by YI-7, and analyzing cell viability (MTT), nuclear staining (Hoechst 33342/PI), and apoptosis-associated proteins using western blot. Results: YI-7 exhibited moderate cytotoxicity in A549 cells (IC₅₀ 137.90±11.48 μM) and dose-dependently inhibited colony formation, with marked suppression at 50 μM. Moreover, YI-7 pretreatment synergistically enhanced cisplatin cytotoxicity in A549 cells, with Combination Index (CI) values <1 and markedly increased apoptosis, particularly at the 2:1 (YI-7:cisplatin) ratio. Mechanistically, the combination strongly up-regulated p53 expression while suppressing Akt signaling compared with either treatment alone. Conclusion: The Res derivative YI-7 potentiates cisplatin-induced apoptosis in human lung cancer cells through increased p53 expression and suppression of the Akt signaling pathway.