Effects of LDD-2269 on the Senescence of Glioblastoma Cells

Abstract

Background and Objective: Cellular senescence manifests as cell cycle arrest accompanied by phenotypic changes such as deregulated metabolism and specialized secretory activity. Senotherapeutics, which exploits cellular senescence for therapeutic purposes, is evolving with the advent of pharmacological interventions such as senolytics and senostatics. LDD-2269 is a benzylidene hydrazine derivative with lysine (K)-specific demethylase 4A activity and its effect on cellular senescence was examined in this study. Materials and Methods: Cellular senescence was measured using senescence-associated beta-galactosidase assay. Western blot and quantitative RT-PCR were employed for the measurement of p21 and IL-8 expression. Results: Treatment with LDD-2269 induced senescence in U87MG glioblastoma cells and primary rat astrocytes. LDD-2269 upregulated the gene expression of p21 and IL-8, which is consistent with the senescent phenotype induction. LDD-2269 also augmented growth inhibition by temozolomide. Conclusion: The results indicate that LDD-2269 can be utilized in cancer senotherapeutics. The combination of LDD-2269 with other senolytics is a promising senotherapeutic strategy in cancer treatment.