Frequent gene hypermethylation in laryngeal cancer cell lines and the resistance to demethylation induction by plant polyphenols

Jarosław Paluszczak; Violetta Krajka-Kuźniak; Zuzanna Małecka; Małgorzata Jarmuż; Magdalena Kostrzewska-Poczekaj; Reidar Grenman; Wanda Baer-Dubowska

doi:10.1016/j.tiv.2010.11.003

Frequent gene hypermethylation in laryngeal cancer cell lines and the resistance to demethylation induction by plant polyphenols

Toxicol In Vitro. 2011 Feb;25(1):213-21. doi: 10.1016/j.tiv.2010.11.003. Epub 2010 Nov 13.

Authors

Jarosław Paluszczak¹, Violetta Krajka-Kuźniak, Zuzanna Małecka, Małgorzata Jarmuż, Magdalena Kostrzewska-Poczekaj, Reidar Grenman, Wanda Baer-Dubowska

Affiliation

¹ Department of Pharmaceutical Biochemistry, Poznań University of Medical Sciences, Poznań, Poland.

PMID: 21078381
DOI: 10.1016/j.tiv.2010.11.003

Abstract

Promoter hypermethylation is one of the mechanisms in the transcriptional inactivation of certain carcinoma - associated genes. In laryngeal cancers hypermethylation of tumor suppressor genes is related to their major risk factors- cigarette smoking and drinking strong alcohols. Since DNA methylation is reversible, modulation of the activity of DNA methyltransferases is an established therapeutic strategy, which can be also applied in cancer chemoprevention. Here, using the MSP procedure, we evaluated the frequency of hypermethylation of RARbeta, RASSF1A, HIN-1, GSTP1, MGMT, VHL and DAPK genes in several laryngeal and other head and neck squamous cell carcinoma cell lines and the effect of various polyphenols on the methylation of RARbeta and MGMT genes in the UT-SCC 42B cell line. Most of the cell lines tested were characterized by the hypermethylation of at least one of the genes analyzed. The most frequently hypermethylated genes were RARbeta and MGMT, while GSTP1 and VHL were not methylated in any of the cell lines. None of the tested compounds, including decitabine used as a reference compound, changed the methylation of RARbeta and MGMT genes. These findings suggest that although hypermethylation of RARbeta and MGMT may be considered as potential epigenetic biomarker, their application as therapeutic/chemopreventive targets requires further studies.

MeSH terms

Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism
Calcium-Calmodulin-Dependent Protein Kinases / genetics
Calcium-Calmodulin-Dependent Protein Kinases / metabolism
Carcinoma, Squamous Cell / drug therapy
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / prevention & control
Cell Line, Tumor
Cell Survival / drug effects
Cinnamates / pharmacology
DNA Methylation / drug effects*
Death-Associated Protein Kinases
Female
Flavonoids / pharmacology*
Gene Silencing / drug effects*
Genes, Tumor Suppressor / drug effects*
Glutathione S-Transferase pi / genetics
Glutathione S-Transferase pi / metabolism
Head and Neck Neoplasms / drug therapy
Head and Neck Neoplasms / metabolism
Humans
Laryngeal Neoplasms / drug therapy
Laryngeal Neoplasms / genetics*
Laryngeal Neoplasms / metabolism
Laryngeal Neoplasms / prevention & control
Male
Phenols / pharmacology*
Polyphenols
Promoter Regions, Genetic / drug effects
RNA, Messenger / metabolism
Receptors, Retinoic Acid / genetics
Receptors, Retinoic Acid / metabolism
Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

Antineoplastic Agents, Phytogenic
Apoptosis Regulatory Proteins
Cinnamates
Flavonoids
Phenols
Polyphenols
RNA, Messenger
Receptors, Retinoic Acid
retinoic acid receptor, beta2, human
GSTP1 protein, human
Glutathione S-Transferase pi
Death-Associated Protein Kinases
Calcium-Calmodulin-Dependent Protein Kinases