Arsenic trioxide inhibits DNA methyltransferase and restores methylation-silenced genes in human liver cancer cells
Abstract
In the present study, we investigated methylation status of the CpG islands of some major tumor suppressor genes both in human hepatocellular carcinoma and liver cancer cell lines and examined whether demethylation by arsenic trioxide (As2O3) could restore their expression in the cell lines. HepG2 and Huh-7 cells were treated with 2 to 10 micromol/L of AS2O3 and/or 1 micromol/L of 5-aza-2'-deoxycytidine for 24, 48, and 72 hours. The methylation status of the CpG island around the promoter regions of p161NK4a, RASSF1A, E cadherin, and GSTP1 was detected by a methylation-specific polymerase chain reaction (MSP). The messenger RNA (mRNA) and protein levels of these genes were determined by quantitative real-time reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemical analyses. The DNA methyltransferase (DNMT) mRNA levels and enzyme activity were also examined. The hypermethylated status of the promoter regions of p16INK4a, RASSF1A, E cadherin, and GSTP1 was observed in 10 (40%), 14 (56%), 6 (24%), and 12 (48%) of 25 patients with hepatocellular carcinoma, respectively. CpG methylation of the p16INK4a, RASSF1A, E cadherin, and GSTP1 genes was correlated to the reduction of mRNA levels in the cell line...Continue Reading
Citations
Related Concepts
Related Feeds
Carcinoma, Hepatocellular
Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.
Cadherins and Catenins
Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.
Adrenocortical Carcinoma
Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.