title: HDAC inhibitors, MS-275 and salermide, potentiates the anticancer effect of EF24 in human pancreatic cancer cells.
abstract: Histone deacetylases (HDACs) play a major role in the regulation of chromatin structure and gene expression by changing acetylation status of histone and non-histone proteins. MS-275 (entinostat, MS) is a well-known benzamide-based HDACI and Salermide (SAL), a reverse amide compound HDACI, have antiproliferative effects on several human cancer cells. In this study, we aimed to investigate the effects of HDACIs (MS and SAL) alone and/or combined use with EF24 (EF), a novel synthetic curcumin analog, on human pancreatic cancer cell line (BxPC-3). In vitro, BxPC-3 cells were exposed to varying concentrations of MS, SAL with or without EF, and their effects on cell viability, acetylated Histone H3 and H4 levels, cytotoxicity, and cleaved caspase 3 levels, and cell cycle distribution were measured. The viability of BxPC-3 cells decreased significantly after treatment with EF, MS and SAL treatments. MS and SAL treatment increased the acetylation of histone H3 and H4 in a dose dependent manner. MS and SAL alone or combined with EF were increased the number of cells in G1 phase. In addition, treatment with agents significantly decreased the ratio of cell in G2/M phase. There were significant dose-dependent increases at cleaved Caspase 3 levels after MS treatment but not after SAL treatment. Our results showed that HDAC inhibitors (MS and SAL), when combined with EF, may effectively reduce pancreatic cancer cell (BxPC-3) progression and stop the cell cycle at G1 phase. Further molecular analyses are needed to understand the fundamental molecular consequences of HDAC inhibition in pancreas cancer cells.
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
authors.forename: Atiye Seda
authors.initials: AS
authors.lastname: Yar Saglam
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Hitit University, Çorum, Turkey.
authors.forename: Akin
authors.initials: A
authors.lastname: Yilmaz
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
authors.forename: Hacer Ilke
authors.initials: HI
authors.lastname: Onen
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Giresun University, Giresun, Turkey.
authors.forename: Ebru
authors.initials: E
authors.lastname: Alp
authors.affiliation: Department of Adult Heamatology, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
authors.forename: Handan
authors.initials: H
authors.lastname: Kayhan
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Besevler, Ankara, Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Ekmekci
keywords: BxPC-3 cells; EF24; HDACI; MS-275; pancreatic cancer; salermide