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Series GSE42490 Query DataSets for GSE42490
Status Public on Dec 01, 2013
Title DNA methyltransferase inhibitor zebularine inhibits human hepatic carcinoma cells proliferation and induces apoptosis.
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary Hepatocellular carcinoma is one of the most common cancers in world wide. During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Zebularine [1-(β-ᴅ-ribofuranosyl)-1,2-dihydropyrimidin-2-one] acts as an inhibitor of DNA methylation and exhibits chemical stability and minimal cytotoxicity both in vitro and in vivo. In this study, we explore the effect and possible mechanism of action of zebularine on hepatocellular carcinoma cell line HepG2. Here, we demonstrated that zebularine exhibited antitumor activity on HepG2 cells by inhibiting cell proliferation and inducing apoptosis. Zebularine treatment down-regulated CDK2 and phosphorylation of retinoblastoma protein (RB), and up-regulated p21WAF/CIP1 and p53. We also found that zebularine treatment up-regulated phosphorylation of p44/42 MAPK. These results suggest that p44/42 MAPK pathway play a role in zebularine induced cell cycle arrest by regulating activity of p21WAF/CIP1 and Rb. Furthermore, we found that zebularine induced apoptosis. Although proapoptotic protein Bax levels were not affected, antiapoptotic protein Bcl-2 level was down-regulated with zebularine treatment. The data in the present study suggest that the action of the double-stranded RNA-dependent protein kinase (PKR) is involved in inducing apoptosis with zebularine. These results provide a novel mechanism of zebularine-induced cell growth arrest and apoptosis in hepatocellular carcinoma.
Overall design Three each independent batches of zebuluarine-treated and control HepG2 cells were subjected to illumina Human methylation 450K Beadchip analysis.
Contributor(s) Nakamura K, Nakabayashi K, Tanoue A
Citation(s) 23320119
Submission date Nov 26, 2012
Last update date Mar 22, 2019
Contact name Kazuhiko Nakabayashi
Organization name National Research Institute for Child Health and Development
Department Department of Maternal-Fetal Biology
Street address 2-10-1 Okura
City Setagaya
State/province Tokyo
ZIP/Postal code 157-8535
Country Japan
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (6)
GSM1040886 HepG2_Z1000_1
GSM1040887 HepG2_Z1000_2
GSM1040888 HepG2_Z1000_3
BioProject PRJNA182141

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE42490_RAW.tar 183.1 Mb (http)(custom) TAR
GSE42490_non_normalized.txt.gz 26.4 Mb (ftp)(http) TXT
Processed data included within Sample table

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