title: Natural Polyphenols Inhibit Lysine-Specific Demethylase-1in vitro.
abstract: Natural polyphenols, such as resveratrol, have beneficial functions on major human diseases such as cancer, diabetes, and cardiovascular disease. Besides acting as antioxidants, some of these polyphenols can also target proteins to modulate specific biological pathways. The lysine-specific histone demethylase LSD1 plays important roles in cell growth, differentiation and nutrient metabolism. Here, we studied the effect of natural polyphenols resveratrol, curcumin, quercetin and analogs on LSD1. Usingin vitroLSD1 enzymatic assays, we show that resveratrol, curcumin and quercetin displayed a potent inhibitory effect on the LSD1 activity and were more potent than the known LSD1 inhibitor trans-2-phenylcyclopropylamine (TCP). The new function of resveratrol, curcumin and quercetin is independent of their antioxidant properties, as other antioxidants had no effect on LSD1 under the similar conditions. In C2C12 fibroblasts, resveratrol and curcumin can efficiently inhibit myogenic expression and differentiation, for which LSD1 is required. Thus, our study has identified LSD1 as a novel target of bioactive natural compounds, such as resveratrol, curcumin and quercetin, and such finding suggests that LSD1 inhibition can at least partially contribute to some of the previously observed beneficial effects of these compounds.
authors: Department of Medicine, Developmental and Molecular Biology, Diabetes Research and Training Center, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx NY 10461, USA.
authors: Arian
authors: A
authors: Abdulla
authors: Xiaoping
authors: X
authors: Zhao
authors: Fajun
authors: F
authors: Yang
keywords: LSD1; curcumin; demethylation; myogenesis; polyphenol; quercetin; resveratrol
references: Chem Biol. 2006 Jun;13(6):563-7
references: 16793513
references: Br J Nutr. 1984 Sep;52(2):179-96
references: 6477859
references: Life Sci. 1997;61(21):2103-10
references: 9395251
references: Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21984-9
references: 19995983
references: Cell. 2007 Feb 9;128(3):505-518
references: 17289570
references: Br J Nutr. 2009 Oct;102(7):1065-74
references: 19402938
references: Physiol Res. 2013;62(1):1-13
references: 23173686
references: Curr Drug Targets. 2011 Mar 1;12(3):332-47
references: 20955148
references: J Agric Food Chem. 2010 Feb 10;58(3):1584-92
references: 19928762
references: Nature. 2007 Nov 29;450(7170):712-6
references: 18046409
references: Nature. 2003 Apr 17;422(6933):735-8
references: 12700765
references: Biochem Biophys Res Commun. 2008 Feb 1;366(1):15-22
references: 18039463
references: J Biol Chem. 2010 Sep 24;285(39):30034-41
references: 20656681
references: Genes Dev. 2010 Jul 1;24(13):1403-17
references: 20595232
references: Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1876-81
references: 19749157
references: Mol Nutr Food Res. 2009 Jan;53(1):115-28
references: 19072742
references: Eur Arch Psychiatry Clin Neurosci. 2006 Aug;256(5):268-73
references: 16927039
references: Am J Chin Med. 2008;36(3):603-13
references: 18543392
references: Nature. 2003 Sep 11;425(6954):191-6
references: 12939617
references: Nature. 2007 Sep 6;449(7158):105-8
references: 17805299
references: Cell Metab. 2007 Oct;6(4):307-19
references: 17908559
references: Biochemistry. 2004 Sep 14;43(36):11417-26
references: 15350128
references: Cell. 2004 Dec 29;119(7):941-53
references: 15620353
references: Biofactors. 2013 Jan-Feb;39(1):101-21
references: 23339042
references: Eur J Pharmacol. 2008 May 13;585(2-3):325-37
references: 18417116
references: J Biol Chem. 2010 Mar 12;285(11):8340-51
references: 20061378
references: Cell Mol Life Sci. 2008 Jun;65(11):1631-52
references: 18324353
references: J Biol Chem. 1998 Aug 21;273(34):21875-82
references: 9705326
references: Clin Chim Acta. 1996 Mar 15;246(1-2):163-82
references: 8814965
references: Nature. 2005 Sep 15;437(7057):436-9
references: 16079795
references: Mol Cell. 2011 Jun 10;42(5):689-99
references: 21596603
references: Immun Ageing. 2010 Jan 17;7(1):1
references: 20205886
references: J Cell Biochem. 2012 Mar;113(3):752-9
references: 22065601
references: Nature. 2005 Sep 15;437(7057):432-5
references: 16079794
references: Biochem Biophys Res Commun. 2010 Oct 22;401(3):327-32
references: 20833138
references: Nat Genet. 2009 Jan;41(1):125-9
references: 19098913
references: J Biol Chem. 2002 Jul 26;277(30):27029-35
references: 12016216
references: Biochem J. 2007 Sep 15;406(3):511-8
references: 17550345
references: Biofactors. 2013 Jan-Feb;39(1):37-55
references: 22996381
references: Ann N Y Acad Sci. 2005 Nov;1056:206-17
references: 16387689
references: Nature. 2006 Nov 16;444(7117):337-42
references: 17086191
references: Nat Rev Mol Cell Biol. 2012 Mar 22;13(4):251-62
references: 22436748
references: Nat Commun. 2012 Mar 27;3:758
references: 22453831
references: Am J Physiol Endocrinol Metab. 2010 Apr;298(4):E751-60
references: 20103737
references: Biochim Biophys Acta. 1985 Apr 25;834(2):275-8
references: 3922423
references: Cell. 2009 Aug 21;138(4):660-72
references: 19703393
references: Trends Biochem Sci. 2008 Apr;33(4):181-9
references: 18343668
references: Acta Pharmacol Sin. 2002 Nov;23(11):1002-6
references: 12421476
references: Curr Pharm Biotechnol. 2010 Dec;11(8):837-48
references: 20874688
references: Nature. 2004 Aug 5;430(7000):686-9
references: 15254550
references: Neurosci Lett. 2003 Dec 11;352(3):203-6
references: 14625020
references: Crit Rev Eukaryot Gene Expr. 2012;22(1):53-9
references: 22339659
references: Am J Epidemiol. 2006 Nov 1;164(9):898-906
references: 16870699
references: Oncol Rep. 2008 Dec;20(6):1553-9
references: 19020741
references: Cell. 2012 Feb 3;148(3):421-33
references: 22304913
references: Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7217-22
references: 17438283
references: Diabetes. 2006 Aug;55(8):2180-91
references: 16873680
references: Cancer Res. 1999 Jun 1;59(11):2596-601
references: 10363980
references: J Biol Chem. 2008 Jul 18;283(29):20015-26
references: 18482975