A Novel Chalcone Polyphenol Inhibits the Deacetylase Activity of SIRT1 and Cell Growth in HEK293T Cells

Journal of Pharmacological Sciences

Maki K. Yamada¹  Mitsutoshi Setou¹  Tomoaki Kahyo¹  Takahiro Hatanaka¹  Shuji Ichikawa² 

[1] Mitsubishi Kagaku Institute of Life Sciences (MITILS), Japan;Mitsubishi Chemical Group Science and Technology Research Center, INC., Japan

关键词: SIRT1;    deacetylation;    inhibitor;    polyphenol;    p53;   

DOI  :  10.1254/jphs.08203FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(37)Cited-By(15)SIRT1 is one of seven mammalian orthologs of yeast silent information regulator 2 (Sir2), and it functions as a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase. Recently, resveratrol and its analogues, which are polyphenols, have been reported to activate the deacetylase activity of SIRT1 in an in vitro assay and to expand the life-span of several species through Sir2 and the orthologs. To find activators or inhibitors to SIRT1, we examined thirty-six polyphenols, including stilbenes, chalcones, flavanones, and flavonols, with the SIRT1 deacetylase activity assay using the acetylated peptide of p53 as a substrate. The results showed that 3,2',3',4'-tetrahydroxychalcone, a newly synthesized compound, inhibited the SIRT1-mediated deacetylation of a p53 acetylated peptide and recombinant protein in vitro. In addition, this agent induced the hyperacetylation of endogenous p53, increased the endogenous p21CIP1/WAF1 in intact cells, and suppressed the cell growth. These results indicated that 3,2',3',4'-tetrahydroxychalcone had a stronger inhibitory effect on the SIRT1-pathway than sirtinol, a known SIRT1-inhibitor. Our results mean that 3,2',3',4'-tetrahydroxychalcone is a novel inhibitor of SIRT1 and produces physiological effects on organisms probably through inhibiting the deacetylation by SIRT1.

【 授权许可】

Unknown