The Effects of Nucleoside Analogues on Promoter Methylation of Selected Tumor Suppressor Genes in MCF-7 and MDA-MB-231 Breast Cancer Cell Lines

Abstract

The effects of 2-chloro-2′-deoxyadenosine, 9-β-D-arabinofuranosyl-2-fluoroadenine, and 5-aza-2′-deoxycytidine on promoter methylation of the selected tumor suppressor genes (i.e., ERα, BRCA1, RARβ2, E-cadherin, PTEN, and APC) were estimated using methylation-sensitive restriction analysis. The studies were carried out in hormone-responsive, low-invasive cell line MCF-7 and hormone-insensitive, highly invasive cell line MDA-MB-231. The results demonstrate an implication of the tested adenosine analogues and 5-aza-dCyd in regulation of DNA methylation process. Moreover, the effects of nucleoside analogues on PTEN promoter methylation suggest distinct mechanism of regulation of the epigenetic DNA modification in low-invasive compared to highly invasive breast cancer cells.

Keywords:

• Nucleoside analogues
• Promoter methylation
• PTEN

Acknowledgments

The research was supported by the Medical University of Lodz (Grant No. 502-12-302) and Ministry of Science and Higher Education (Grant No. 2 P05A 036 30). MCF-7 cell line was kind gift from Dr. Marek Rozalski (Department of Biology and Biotechnology, Medical University of Lodz, Poland).

Notes

^a The inhibition of methylation was expressed as a percentage of methylation of digested control DNA from cells cultured without drugs.

^a The inhibition of methylation was expressed as a percentage of methylation of digested control DNA from cells cultured without drugs.