title: In silico and biochemical analyses identify quinone reductase 2 as a target of piceatannol.
abstract: To obtain information on anti-prostate cancer (CaP) activities of piceatannol, a metabolite biotransformed from resveratrol by cytochrome P450 CYP1B, CWR22Rv1 cells were incubated with increasing dose of piceatannol. Proliferation and apoptosis assays in exposed cells showed that piceatannol produced inhibition comparable to resveratrol. To determine whether quinone reductase 2 (NQO2) plays a role in the observed effects, in silico analysis was performed. Piceatannol interacted with NQO2 at the same site as resveratrol forming hydrogen bond with asparagine-161 (ASN161). NQO2 mediated anti-CaP effects of piceatannol were also tested and supported by the attenuation of anti-proliferative activity and reduction in extent of inhibition of NQO2 activity by piceatannol in NQO2-knockdown cells relative to NQO2- expressing cells, and by the copious expression of CYP1B in CWR22Rv1 cells. These results show that NQO2 is an intracellular target for piceatannol, suggesting that CaP prevention by resveratrol may be partially attributed to its conversion to piceatannol.
authors.affiliation: Research Associate Professor, Room 133, Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA. Tze-chen_Hsieh@nymc.edu.
authors.forename: Tze-Chen
authors.initials: TC
authors.lastname: Hsieh
authors.forename: Dylan John
authors.initials: DJ
authors.lastname: Bennett
authors.forename: Yong-Syu
authors.initials: YS
authors.lastname: Lee
authors.forename: Erxi
authors.initials: E
authors.lastname: Wu
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D065633:Cytochrome P-450 CYP1B1; D006801:Humans; D062105:Molecular Docking Simulation; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011808:Quinone Reductases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
chemical_list: D034741:RNA, Small Interfering; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases; D000077185:Resveratrol