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 cells

作者：Stefanska Barbara^*; Salame Patrick; Bednarek Andrzej; Fabianowska Majewska Krystyna

来源：British Journal of Nutrition, 2012, 107(6): 781-790.

DOI：10.1017/S0007114511003631

• Vitamins
• Phyto-oestrogens
• Promoter methylation
• Chemoprevention
• Epigenetic therapy

Aberrations in DNA methylation patterns have been reported to be involved in driving changes in the expression of numerous genes during carcinogenesis and have become promising targets for chemopreventive action of natural compounds. In the present study, we investigated the effects of all-trans retinoic acid (ATRA), vitamin D-3 and resveratrol alone and in combination with adenosine analogues, 2-chloro-2'-deoxyadenosine (2CdA) and 9-beta-D-arabinosyl-2-fluoroadenine (F-ara-A), on the methylation and expression of phosphatase and tensin homologue (PTEN) 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-3 and resveratrol possess high efficacy in the reduction of PTEN promoter methylation. It was associated with PTEN induction as well as DNA methyltransferase down-regulation and p21 up-regulation after treatments with vitamin D-3 and resveratrol, suggesting a complex regulation of the DNA methylation machinery. Vitamin D-3 and resveratrol improved the inhibitory effects of 2CdA and F-ara-A on PTEN methylation in MCF-7 cells; however, only the combined action of vitamin D-3 and 2CdA boosted the induction of PTEN expression, suggesting a cooperation of these compounds in additional processes driving changes in PTEN expression. In contrast, in highly invasive MDA-MB-231 cells, only vitamin D-3 reduced PTEN 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.

• 出版日期2012-3