Renieramycin T Derivative DH_22 Induces p53-dependent Apoptosis in Lung Cancer Cells

Background/Aim: Targeting apoptotic pathways has been identified as a promising strategy for the treatment of lung cancer. We synthesized a new derivative of renieramycin T (RT), named DH_22, and examined its anti-cancer activities in human lung cancer cells. Materials and Methods: The RT derivative DH_22 was chemically modified from RT. The apoptosis-inducing effect was evaluated in A549 cells by annexin V-FITC/PI staining and nuclear staining assay (Hoechst/PI). In addition, the molecular pathway was analyzed by western blot analysis. Results: In the cell viability and nuclear staining tests, DH_22 was discovered to be cytotoxic with an IC50 of 13.27 mu M; it induced apoptosis of lung cancer cells. Regarding the mechanism, DH_22 contributed to the activation of p53 -dependent apoptosis and decreased the cellular level of c-Myc. The p53-dependent mechanism was indicated by an increase in p53, an induction of the pro-apoptotic Bax protein, and a decrease in the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein. Conclusion: DH_22 has great potential for further development as a new anticancer drug.