Resveratrol Derivatives Inhibit Pro-survival Akt Signaling Pathway in Lung Cancer.

Abstract

Background/aim: Akt signaling promotes cancer survival and therapy resistance. This study aimed to modify and improve resveratrol's efficacy by enhancing apoptosis induction in non-small cell lung cancer.

Materials and methods: Molecular docking analysis was used to investigate the binding between resveratrol derivatives and the Akt protein. Western blot analysis evaluated the levels of apoptosis markers and signaling proteins.

Results: Resveratrol derivative, RD4 (4-(3-hydroxy-4-methoxyphenethyl)-2,6-dimethoxyphenol), shows binding potential to the allosteric site of Akt. After treatment of H460 cells with RD4 for 24 h, increased apoptosis and decreased levels of phosphorylated-Akt (p-Akt) protein were observed. Moreover, the levels of pro-apoptotic protein Bax and cleaved PARP were elevated, while those of the anti-apoptotic protein Bcl-2 were decreased. However, RD2 exhibited moderate effects at high concentrations and RD3 elevated p-Akt expression while exhibiting no apoptotic activity.

Conclusion: RD4 suppresses Akt pathways by binding at the allosteric site of Akt. These findings provide a rationale for the design and optimization of novel Akt targeting agents for non-small cell lung cancer treatment.