title: Regulation of cancer-related genes - Cyp1a1, Cyp1b1, Cyp19, Nqo1 and Comt - expression in β-naphthoflavone-treated mice by miroestrol.
abstract: OBJECTIVE
  The effects of miroestrol (MR), an active phytoestrogen from Pueraria candollei var. mirifica, on expression of cancer-related genes were determined.
  
  
  METHODS
  Seven-week-old female ICR mice (n = 5 each) were subcutaneously administered estradiol (E2, 0.5 mg/kg/day) or MR (0.5 or 5 mg/kg/day) daily for 7 days. Some were given ER or MR in combination with β-naphthoflavone (BNF, 30 mg/kg/day) for the last 3 days. The expression of cancer-related genes including cytochrome P450 1A (Cyp1a), cytochrome P450 1B1 (Cyp1b1), aromatase P450 (Cyp19), NAD(P)H: quinone oxidoreductase 1 (Nqo1) and catechol-O-methyltransferase (Comt) were evaluated.
  
  
  RESULTS
  In the presence of BNF, MR suppressed hepatic CYP1A1 activity and CYP1A2 activity, expression of CYP1B1 mRNA and expression of CYP1A1/2 and CYP1B1 protein. E2, by contrast, did not. MR restored expression levels of hepatic NQO1 and uterine COMT in BNF-treated mice. Furthermore, MR increased expression of uterine CYP19 to the same extent as E2.
  
  
  CONCLUSIONS
  MR may be superior to E2 as it downregulates expression of CYP1. Moreover, MR normalized expression of both NQO1 and COMT, the protective enzymes, in murine liver and uteri. These results support the use of MR as an alternative supplement for menopausal women, MR having the extra benefit of reducing cancer risk.
authors.affiliation: Faculty of Medicine, Mahasarakham University, Maha Sarakham, Thailand.|Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Waranya
authors.initials: W
authors.lastname: Chatuphonprasert
authors.affiliation: Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Jarukamjorn
authors.affiliation: Research Group for Pharmaceutical Activities of Natural Products using Pharmaceutical Biotechnology (PANPB), Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Waraporn
authors.initials: W
authors.lastname: Putalun
mesh_terms: D000818:Animals; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics / Q000378:metabolism*; D000072496:Cytochrome P450 Family 19 / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008813:Mice, Inbred ICR; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D048789:Phytoestrogens / Q000494:pharmacology* / Q000633:toxicity; D013256:Steroids / Q000494:pharmacology* / Q000633:toxicity; D014599:Uterus / Q000187:drug effects* / Q000201:enzymology; D019324:beta-Naphthoflavone / Q000494:pharmacology*
chemical_list: D048789:Phytoestrogens; D013256:Steroids; C571572:miroestrol; D004958:Estradiol; D019324:beta-Naphthoflavone; C585498:Cyp1b1 protein, mouse; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D000072496:Cytochrome P450 Family 19; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; C000593198:COMT protein, mouse; D002394:Catechol O-Methyltransferase
keywords: Pueraria mirifica; cancer risk; estrogenic activity