Article ID Journal Published Year Pages File Type
2130937 Experimental Cell Research 2012 10 Pages PDF
Abstract

Recent reports have showed that histone deacetylase (HDAC) inhibitor resulted in multidrug resistance (MDR) to other chemotherapeutic agents. However, the molecular mechanisms of Class I HDACs on MDR regulation are poorly understood. In this study, HDAC1 and HDAC2 acted as enhancers to intensify the chemosensitivities of anti-cancer drugs via reducing the expression levels of P-gp, MRP1 and MRP2. Furthermore, the dissociation of HDAC1 and HDAC2 led to transcriptional regulation of P-gp expression via the recruitment of p300, PCAF and NF-Y to the P-gp promoter region, which subsequently increased the level of the active gene marker, hyperacetylated histone H3. In parallel, selective inhibition of HDAC1 and HDAC2 induced the recruitment of p300, PCAF, NF-Y via acetylation of Sp1. Thus, our findings showed HDAC1 and 2 regulated P-gp expression through dynamic changes in chromatin structure and transcription factor association within the promoter region.

Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Cancer Research
Authors
, , , , ,