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In the present study, we investigated the effects of all-<jats:italic>trans<\/jats:italic>retinoic acid (ATRA), vitamin D<jats:sub>3<\/jats:sub>and resveratrol alone and in combination with adenosine analogues, 2-chloro-2\u2032-deoxyadenosine (2CdA) and 9-\u03b2-<jats:sc>d<\/jats:sc>-arabinosyl-2-fluoroadenine (F-ara-A), on the methylation and expression of phosphatase and tensin homologue (<jats:italic>PTEN<\/jats:italic>) tumour suppressor gene in MCF-7 and MDA-MB-231 breast cancer cells. The present results showed that in non-invasive MCF-7 cells, ATRA, vitamin D<jats:sub>3<\/jats:sub>and resveratrol possess high efficacy in the reduction of<jats:italic>PTEN<\/jats:italic>promoter methylation. It was associated with<jats:italic>PTEN<\/jats:italic>induction as well as DNA methyltransferase down-regulation and<jats:italic>p21<\/jats:italic>up-regulation after treatments with vitamin D<jats:sub>3<\/jats:sub>and resveratrol, suggesting a complex regulation of the DNA methylation machinery. Vitamin D<jats:sub>3<\/jats:sub>and resveratrol improved the inhibitory effects of 2CdA and F-ara-A on<jats:italic>PTEN<\/jats:italic>methylation in MCF-7 cells; however, only the combined action of vitamin D<jats:sub>3<\/jats:sub>and 2CdA boosted the induction of<jats:italic>PTEN<\/jats:italic>expression, suggesting a cooperation of these compounds in additional processes driving changes in<jats:italic>PTEN<\/jats:italic>expression. In contrast, in highly invasive MDA-MB-231 cells, only vitamin D<jats:sub>3<\/jats:sub>reduced<jats:italic>PTEN<\/jats:italic>methylation and induced its expression without notable effects in combined treatments. The present results suggest that natural compounds can find application in epigenetic anticancer therapy aimed at inhibition of promoter methylation of tumour suppressor genes and induction of their expression at early stages of carcinogenesis.<\/jats:p>","DOI":"10.1017\/s0007114511003631","type":"journal-article","created":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T09:47:40Z","timestamp":1312192060000},"page":"781-790","source":"Crossref","is-referenced-by-count":97,"title":["Comparative effects of retinoic acid, vitamin D and resveratrol alone and in combination with adenosine analogues on methylation and expression of phosphatase and tensin homologue tumour suppressor gene in breast cancer 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