A novel histone deacetylase inhibitor induces proliferation inhibition of human colon cancer cells
10.7644/j.issn.1674-9960.2014.09.014
- VernacularTitle:新型组蛋白去乙酰化酶抑制剂对结肠癌细胞的增殖抑制作用
- Author:
Chenchen JIANG
;
Zhixin QIAO
;
Shuzhen ZHANG
;
Suping REN
;
Chunyan WANG
;
Weijing LI
;
Xuanlin WANG
;
Min HE
;
Qiyuan GUI
;
Xuejie DING
;
Yanbing WANG
;
Yu WANG
;
Lihua YANG
;
Fumei WANG
;
Changjin ZHU
;
Chengze YU
;
Qun YU
- Publication Type:Journal Article
- Keywords:
colon neoplasms;
histone deacetylase inhibitor;
JZ004;
apoptosis;
membrane potential,mitochondrial
- From:
Military Medical Sciences
2014;(9):708-713
- CountryChina
- Language:Chinese
-
Abstract:
Objective To examine the anticancer effect of a novel histone deacetylase inhibitor (HDACi), JZ004, on colon cancer cells HCT-8 and HT-29, and to investigate the molecular mechanisms of proliferation inhibition and apoptosis induction of cancer cells treated by JZ 004.Methods Colon cancer cells were treated with a series of concentrations of JZ004 .MTT assay was used to detect the proliferation of cancer cells .The cell cycle distribution and apoptosis were deter-mined by flow cytometry .Rhodamine 123 and DCFH-DA were applied to detect the mitochondrial membrane potential (ΔΨm) and reactive oxygen species ( ROS) production.The protein expressions of acetyl-histone H3, p21, cyclin-dependent kinase(CDK)4, Bcl-2, Mcl-1 and Bax were assayed by Western blotting .Results JZ004 was found to inhibit proliferation and induce apoptosis of colon cancer cells in a time-and dose-dependent manner , accompanied by a dose-dependent hyperacetylation of histone H3.JZ004 induced the cancer cell arrest in G 0/G1 phase by increasing the expres-sion level of p21 while CDK4 was downregulated .JZ004 also increased cellular ROS production and reduced ΔΨm by regu-lating the expressions of Bcl-2 family proteins .Conclusion As a novel HDACi , JZ004 effectively inhibits proliferation and increases ROS production to induce apoptosis of colon cancer cells .The results indicate that JZ004 is a potential compound to be developed as an anti-colon cancer agent for clinic application .
