title: Role of CYP1A1 in the biological activity of methylated resveratrol analogue, 3,4,5,4'-tetramethoxystilbene (DMU-212) in ovarian cancer A-2780 and non-cancerous HOSE cells.
abstract: The role of CYP1A1 and CYP1B1 enzymes in the biotransformation and biological activity of the methylated resveratrol analogue, 3,4,5,4'-tetramethoxystilbene (DMU-212) is still elusive. Our recently published data have shown that one of the metabolites of DMU-212, 3'-hydroxy-3,4,5,4'-tetramethoxystilbene (DMU-214) exerts more potent cytotoxic effects in A-2780 ovarian cancer cell line, as compared to the parent compound. Hence, this study aims to elucidate whether the biological activity of DMU-212 is related to its biotransformation to DMU-214. Furthermore, we aimed to assess which enzymes of CYP1 family are involved in the biotransformation of DMU-212. The human ovarian cancer cell lines A-2780, A-2780CYP1A1(-) and non-cancerous human ovarian surface epithelial (HOSE) cells were employed in the present study. In contrary to other authors' suggestions we have found that CYP1A1 is the major enzyme of CYP1 family involved in the metabolic activation of DMU-212. Since the distinctly weaker anti-proliferative effects of DMU-212 against HOSE and A-2780CYP1A1(-) cells have been associated with the lack of the expression of CYP1A1, we suggest that the biological activity of the parent compound may be related to its metabolic activation to DMU-214 and the level of this enzyme.
authors.affiliation: Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30 St., PL-60-631 Poznan, Poland. Electronic address: hanna.piotrowska@ump.edu.pl.
authors.forename: Hanna
authors.initials: H
authors.lastname: Piotrowska-Kempisty
authors.affiliation: Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6 St., PL-60-780 Poznan, Poland. Electronic address: aklupczynska@ump.edu.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Klupczyńska
authors.affiliation: Department of Clinical Immunology, Poznan University of Medical Sciences, Rokietnicka 5d St., PL-60-806 Poznan, Poland,. Electronic address: trzybulskadorota@gmail.com.
authors.forename: Dorota
authors.initials: D
authors.lastname: Trzybulska
authors.affiliation: Radiobiology Laboratory, Department of Medical Physics, Greater Poland Cancer Centre, Garbary 15 St., PL-61-866, Poznan, Poland,. Electronic address: katarzyna.kulcenty@wco.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kulcenty
authors.affiliation: Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6 St., PL-60-780 Poznan, Poland. Electronic address: sulejsuchomska@ump.edu.pl.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Sulej-Suchomska
authors.affiliation: Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30 St., PL-60-631 Poznan, Poland. Electronic address: kucinska@umed.poznan.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Kucińska
authors.affiliation: Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6 St., PL-60-780 Poznan, Poland. Electronic address: rmikstac@ump.edu.pl.
authors.forename: Renata
authors.initials: R
authors.lastname: Mikstacka
authors.affiliation: Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6 St., PL-60-780 Poznan, Poland. Electronic address: mwierzch@ump.edu.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wierzchowski
authors.affiliation: Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30 St., PL-60-631 Poznan, Poland. Electronic address: marek.murias@ump.edu.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Murias
authors.affiliation: Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Święcickiego 4 St., PL-60-781 Poznan, Poland. Electronic address: baerw@ump.edu.pl.
authors.forename: Wanda
authors.initials: W
authors.lastname: Baer-Dubowska
authors.affiliation: Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6 St., PL-60-780 Poznan, Poland. Electronic address: zjk@ump.edu.pl.
authors.forename: Zenon
authors.initials: Z
authors.lastname: Kokot
authors.affiliation: Department of Toxicology, Poznan University of Medical Sciences, Dojazd 30 St., PL-60-631 Poznan, Poland. Electronic address: liebert@ump.edu.pl.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Jodynis-Liebert
mesh_terms: D065767:Activation, Metabolic; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D006900:Hydroxylation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D013267:Stilbenes / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection
chemical_list: C482492:3,4,5,4'-tetramethoxystilbene; D000970:Antineoplastic Agents; D013267:Stilbenes; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1
keywords: CYP1A1; DMU-212; DMU-214; Metabolic activation; Resveratrol