Bioreductive activation of catechol estrogen-ortho-quinones: aromatization of the B ring in 4-hydroxyequilenin markedly alters quinoid formation and reactivity

Carcinogenesis
L ShenJ L Bolton

Abstract

There is a clear association between excessive exposure to estrogens and the development of cancer in several tissues including breast and endometrium. The risk factors for women developing these cancers are all associated with longer estrogen exposure, as may be facilitated by early menses, late menopause and long-term estrogen replacement therapy. Equilenin (1,3,5(10),6,8-estrapentaen-3-ol-17-one) or its 17-hydroxylated analogs make up 15% of the most widely prescribed estrogen replacement formulation, Premarin, and yet there is very little information on the human metabolism of these estrogens. In this study, we synthesized the catechol metabolite of equilenin, 4-hydroxyequilenin, and examined how aromatization of the B ring affects the formation and reactivity of the o-quinone (3,5-cyclohexadien-1,2-dione). 4-Hydroxyequilenin-o-quinone is much more redox-active and longer-lived than the endogenous catechol estrone-o-quinones, which suggests that the mechanism(s) of toxicity of the former could be quite different. Interestingly, the rate of reduction of the 4-hydroxyequilenin-o-quinone is increased at least 13-fold in the presence of NAD(P)H:quinone oxidoreductase (DT-diaphorase). Once NADH is consumed however, the catechol ...Continue Reading

Citations

Feb 17, 2001·Rapid Communications in Mass Spectrometry : RCM·D WilliamsM K Young
Sep 19, 2006·Chemical Research in Toxicology·Tamara S DowersJudy L Bolton
Jun 15, 2010·Chemical Research in Toxicology·Kuan-Wei PengGregory R J Thatcher
May 31, 2012·Chemical Research in Toxicology·Bradley T MichalsenJudy L Bolton
Dec 7, 2007·Chemical Research in Toxicology·Judy L Bolton, Gregory R J Thatcher
Jul 1, 2008·Chemical Research in Toxicology·R Esala P ChandrasenaGregory R J Thatcher
Aug 5, 2009·Rheumatology·Wahid Ali KhanHarvinder S Chabbra
Sep 20, 2011·Menopause : the Journal of the North American Menopause Society·Ingrid ZitňanováZdeňka Duračková
Aug 21, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shuijie ShenJiang Zheng
May 26, 2011·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Philip S CrookeFritz F Parl
Apr 18, 2008·Chemical Research in Toxicology·Shuang DingSuse Broyde
Oct 12, 2010·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Fagen ZhangMichael J Bartels
Jun 25, 2013·Drug Discovery Today. Disease Mechanisms·Monica M MontanoSmitha Sripathy
Sep 26, 2007·Free Radical Biology & Medicine·Nilesh W GaikwadErcole L Cavalieri
Sep 17, 2011·Chemistry & Biodiversity·Michael P StoneGanesh Shanmugam
Dec 21, 2004·Chemico-biological Interactions·Erika L AbelDavid L Eaton
Sep 13, 2016·Chemical Research in Toxicology·Judy L Bolton, Tareisha Dunlap
Mar 23, 2021·Frontiers in Molecular Biosciences·Simona De SummaRosamaria Pinto
Mar 29, 2021·Redox Biology·David Ross, David Siegel
Aug 4, 2007·Chemical Research in Toxicology·Jennifer L BillinskyEd S Krol
May 11, 2007·Journal of Medicinal Chemistry·Zhihui QinGregory R J Thatcher

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.