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[Cancer Research 58, 2269-2277, June 1, 1998]
© 1998 American Association for Cancer Research
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Is 2-Methoxyestradiol an Endogenous Estrogen Metabolite That Inhibits Mammary Carcinogenesis?

Bao Ting Zhu1 and Allan H. Conney2

Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers-The State University of New Jersey, Piscataway, New Jersey 08854-8020

Catechol estrogens (2- or 4-hydroxyestradiol and 2- or 4-hydroxyestrone) are chemically reactive estrogen metabolites that are O-methylated to less polar monomethyl ethers by catechol-O-methyltransferase, an enzyme present in many tissues such as the liver, kidney, brain, placenta, uterus, and mammary gland. In the present report, we review recent studies on the antitumorigenic and antiangiogenic effects of exogenously administered 2-methoxyestradiol in vitro and in vivo. We also discuss data that suggest that endogenous formation of 2-methoxyestradiol (and its 2-hydroxyestradiol precursor) may have a protective effect on estrogeninduced cancers in target organs. Although the molecular mechanism of action of 2-methoxyestradiol is not clear, we suggest that some unique effects of 2-methoxyestradiol may be mediated by a specific intracellular effector or receptor that is refractory to the parent hormone, estradiol. Additional research is needed to identify factors that regulate the metabolic formation and disposition of 2-methoxyestradiol in liver and in target cells and to evaluate the effects of modulating 2-methoxyestradiol formation on estrogen-induced carcinogenesis.

1 To whom requests for reprints should be addressed, at Rutgers University, College of Pharmacy, Laboratory for Cancer Research, Department of Chemical Biology, 164 Frelinghuysen Road, Piscataway, NJ 08854-8020. Fax: (732) 445-0687; E-mail: baoting@rci.rutgers.edu.

2 William M. and Myrle W. Garbe Professor of Cancer and Leukemia Research.

Received 1/16/98. Accepted 3/26/98.




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L.-J. W. Lu, M. Cree, S. Josyula, M. Nagamani, J. J. Grady, and K. E. Anderson
Increased Urinary Excretion of 2-Hydroxyestrone but not 16{{alpha}}-Hydroxyestrone in Premenopausal Women during a Soya Diet Containing Isoflavones
Cancer Res., March 1, 2000; 60(5): 1299 - 1305.
[Abstract] [Full Text]

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 Cancer Epidemiol. Biomarkers Prev.Home page
W. Zheng, D.-W. Xie, F. Jin, J.-R. Cheng, Q. Dai, W.-Q. Wen, X.-O. Shu, and Y.-T. Gao
Genetic Polymorphism of Cytochrome P450-1B1 and Risk of Breast Cancer
Cancer Epidemiol. Biomarkers Prev., February 1, 2000; 9(2): 147 - 150.
[Abstract] [Full Text]

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 Cancer Res.Home page
C.-S. Huang, H.-D. Chern, K.-J. Chang, C.-W. Cheng, S.-M. Hsu, and C.-Y. Shen
Breast Cancer Risk Associated with Genotype Polymorphism of the Estrogen-metabolizing Genes CYP17, CYP1A1, and COMT: A Multigenic Study on Cancer Susceptibility
Cancer Res., October 1, 1999; 59(19): 4870 - 4875.
[Abstract] [Full Text] [PDF]

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 Clin. Cancer Res.Home page
G. Schumacher, M. Kataoka, J. A. Roth, and T. Mukhopadhyay
Potent Antitumor Activity of 2-Methoxyestradiol in Human Pancreatic Cancer Cell Lines
Clin. Cancer Res., March 1, 1999; 5(3): 493 - 499.
[Abstract] [Full Text] [PDF]


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