All-trans retinoic acid induces cellular senescence by up-regulating levels of p16 and p21 via promoter hypomethylation

Riferimento: 
Biochem Biophys Res Commun. 2011 Sep 2;412(3):500-5.
Autori: 
Lim JS, Park SH, Jang KL.
Fonte: 
Biochem Biophys Res Commun. 2011 Sep 2;412(3):500-5.
Anno: 
2011
Azione: 
L'acido all-trans retinoico (ATRA) può essere considerato come un farmaco epigenetico nella terapia del cancro.
Target: 
ATRA/epi-farmaco.

ABSTRACT
All-trans retinoic acid (ATRA) induces cellular senescence via up-regulation of p16 and p21; however, the action mechanism of ATRA is unknown. Here, we show that ATRA induces promoter hypomethylation of p16 and p21 via down-regulation of DNA methyltransferases 1, 3a, and 3b to facilitate binding of Ets1/2 to the p16 promoter and p53 to the p21 promoter, resulting in up-regulation of their expression and subsequent induction of cellular senescence in HepG2 cells. These effects were mediated by retinoic acid receptor β₂ whose promoter was also hypomethylated in the presence of ATRA. Therefore, ATRA can be considered as an epi-drug in cancer therapy.

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