TY - JOUR T1 - The HDAC1 Inhibitor CBUD-1001 Enhances TRAIL-induced Apoptosis in Colorectal Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 4353 LP - 4364 DO - 10.21873/anticanres.15240 VL - 41 IS - 9 AU - MIN WOO SHIN AU - SE LIM KIM AU - HEE CHAN YANG AU - SUNG KYUN YIM AU - SEUNG YOUNG SEO AU - SOO TEIK LEE AU - HEE-KWON KIM AU - SANG-WOOK KIM Y1 - 2021/09/01 UR - http://ar.iiarjournals.org/content/41/9/4353.abstract N2 - Background/Aim: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-tumor agent. However, resistance to TRAIL has been reported in a number of clinical trials. In this study, we investigated the molecular mechanisms by which a novel histone deacetylase (HDAC) inhibitor, CBUD-1001, sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis. Materials and Methods: Apoptotic cell death induced by CBUD-1001 and/or TRAIL was assessed on human CRC cells using the MTT assay, FACS analysis and nuclei staining. The involved molecular mechanisms were explored through western blotting analysis. Results: We demonstrated that combined with CBUD-1001, TRAIL significantly enhanced TRAIL-induced apoptosis in CRC cells via mitochondria-mediated pathways. We also found that hyper-acetylation of histone by CBUD-1001 treatment leads to up-regulation of death receptor (DR) 5 in a dose- and time-dependent manner. Furthermore, we identified that enhanced sensitivity to TRAIL by combination with CBUD-1001 depends on the MAPK/CHOP axis, being a key mediator of DR5. Conclusion: A novel HDAC inhibitor CBUD-1001 sensitizes TRAIL-induced apoptosis via up-regulation of DR5, and that CBUD-1001 and TRAIL combination treatment offers an effective strategy to overcome TRAIL resistance in CRC cells. ER -