Potential vascular actions of 2-methoxyestradiol

Trends in Endocrinology and Metabolism

Volumn 20, Issue 8, 2009, Pages 374-379

  Dubey, Raghvendra K ^a,b,c   Jackson, Edwin K ^c  

^a Clinic for Reproductive Endocrinology   (Switzerland)

^b UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 HYDROXYESTRADIOL; 2 METHOXYESTRADIOL; ALPHA TOCOPHEROL; CATECHOL ESTROGEN; CHOLESTEROL; ESTRADIOL; ESTROGEN RECEPTOR;

ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; ARTICLE; ATHEROSCLEROSIS; BRAIN ISCHEMIA; CARDIOVASCULAR DISEASE; CELL PROLIFERATION; CHOLESTEROL BLOOD LEVEL; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENTIATION; DRUG RECEPTOR BINDING; DRUG SAFETY; HEART PROTECTION; HORMONE ACTION; HUMAN; HYPERTENSION; IC 50; INFLAMMATION; KIDNEY DISEASE; NONHUMAN; PREECLAMPSIA; PRIMARY PREVENTION; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RENAL PROTECTION; VASCULAR ENDOTHELIUM; VASCULAR SMOOTH MUSCLE;

ANIMALS; CARDIOVASCULAR DISEASES; ESTRADIOL; HUMANS; MODELS, BIOLOGICAL; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; NEOVASCULARIZATION, PATHOLOGIC; TUBULIN MODULATORS;

EID: 70349473165     PISSN: 10432760     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tem.2009.04.007     Document Type: Article

References (50)

1. Zhu B.T., and Conney A.H. Is 2-methoxyestradiol an endogenous estrogen metabolite that inhibits mammary carcinogenesis?. Cancer Res. 58 (1998) 2269-2277
2. Dubey R.K., et al. Cardiovascular pharmacology of estradiol metabolites. J. Pharmacol. Exp. Therapeutics 308 (2004) 403-409
3. Lakhani N.J., et al. Pharmacokinetics, pharmacodynamics and drug metabolism - Characterization of in vitro and in vivo metabolic pathways of the investigational anticancer agent, 2-methoxyestradiol. J. Pharm. Sci. 96 (2007) 1821-1831
4. Dubey R.K., et al. 2-Methoxyestradiol: A potential treatment for multiple proliferative disorders. Endocrinology 148 (2007) 4125-4127
5. Ho A., et al. SAR studies of 2-methoxyestradiol and development of its analogs as probes of anti-tumor mechanisms. Bioorg. Med. Chem. Lett. 16 (2006) 3383-3387
6. Barchiesi F., et al. 2-methoxyestradiol, an estradiol metabolite, inhibits neointima formation and smooth muscle cell growth via double blockade of the cell cycle. Circ. Res. 99 (2006) 266-274
7. Dubey R.K., and Jackson E.K. Cardiovascular protective effects of 17beta-estradiol metabolites. J. Appl. Physiol. 91 (2001) 1868-1883
8. Bourghardt J., et al. The endogenous estradiol metabolite 2-methoxyestradiol reduces atherosclerotic lesion formation in female apolipoprotein E-deficient mice. Endocrinology 148 (2007) 4128-4132
9. Sattler M., et al. 2-methoxyestradiol alters cell motility, migration, and adhesion. Blood 102 (2003) 289-296
10. Kurokawa A., et al. 2-methoxyestradiol reduces monocyte adhesion to aortic endothelial cells in ovariectomized rats. Endocr. J. 54 (2007) 1027-1031
11. Cramer T., et al. HIF-1α is essential for myeloid cell-mediated inflammation. Cell 112 (2003) 645-657
12. Seeger H., et al. Effect of estradiol metabolites on prostacyclin synthesis in human endothelial cell cultures. Life Sci. 65 (1999) PL167-PL170
13. Gui X.-L., et al. Inhibition of rat aortic smooth muscle contraction by 2-methoxyestradiol. Am. J. Physiol. Heart Circ. Physiol. 295 (2008) H1935-H1942
14. Tsukamoto A., et al. 2-methoxyestradiol, an endogenous metabolite of estrogen, enhances apoptosis and beta-galactosidase expression in vascular endothelial cells. Biochem. Biophys. Res. Commun. 248 (1998) 9-12
15. Kanasaki K., et al. Deficiency in catechol-O-methyltransferase and 2-methoxyestradiol is associated with pre-eclampsia. Nature 453 (2008) 1117-1121
16. Tofovic S.P., et al. 2-hydroxyestradiol attenuates the development of obesity, the metabolic syndrome, and vascular and renal dysfunction in obese ZSF1 rats. J. Pharmacol. Exp. Ther. 299 (2001) 973-977
17. Fotsis T., et al. The endogenous estrogen metabolite 2-methoxyestradiol inhibits angiogenesis and suppresses tumor-growth. Nature 368 (1994) 237-239
18. Masi C.M., et al. Estrogen metabolites and systolic blood pressure in a population-based sample of postmenopausal women. J. Clin. Endocrinol. Metab. 91 (2006) 1015-1020
19. Tofovic S.P., et al. 2-Methoxyestradiol mediates the protective effects of estradiol in monocrotaline-induced pulmonary hypertension. Vasc. Pharmacol. 45 (2006) 358-367
20. Tofovic S.P., et al. Estradiol metabolites attenuate monocrotaline-induced pulmonary hypertension in rats. J. Cardiovasc. Pharmacol. 46 (2005) 430-437
21. Tofovic S.P., et al. Estradiol metabolites attenuate renal and cardiovascular injury induced by chronic nitric oxide synthase inhibition. J. Cardiovasc. Pharmacol. 46 (2005) 25-35
22. Chen C.H., et al. Multiple effects of 2ME2 and D609 on the cortical expression of HIF-1 alpha and apoptotic genes in a middle cerebral artery occlusion-induced focal ischemia rat model. J. Neurochem. 102 (2007) 1831-1841
23. Luttun A., and Carmeliet P. Soluble VEGF receptor Flt1: the elusive preeclampsia factor discovered. J. Clin. Invest. 111 (2003) 600-602
24. Barchiesi F., et al. Methoxyestradiols mediate estradiol-induced antimitogenesis in human aortic SMCs. Hypertension 39 (2002) 874-972
25. Dubey R.K., et al. Methoxyestradiols mediate the antimitogenic effects of estradiol on vascular smooth muscle cells via estrogen receptor-independent mechanisms. Biochem. Biophys. Res. Commun. 278 (2000) 27-33
26. Dubey R.K., et al. Estrogen and tamoxifen metabolites protect smooth muscle cell membrane phospholipids against peroxidation and inhibit cell growth. Circ. Res. 84 (1999) 229-239
27. Harada N., et al. Localized expression of aromatase in human vascular tissues. Circ. Res. 84 (1999) 1285-1291
28. Zhao W., et al. Constitutive and inducible expression of cytochrome P4501A1 and P4501B1 in human vascular endothelial and smooth muscle cells. In Vitro Cell Dev. Biol. Anim. 34 (1998) 671-673
29. Dubey R.K., et al. CYP450- and COMT-derived estradiol metabolites inhibit activity of human coronary artery SMCs. Hypertension 41 (2003) 807-813
30. Zacharia L.C., et al. Catecholamines abrogate antimitogenic effects of 2-hydroxyestradiol on human aortic vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol. 21 (2001) 1745-1750
31. Dubey R.K., et al. Medroxyprogesterone abrogates the inhibitory effects of estradiol on vascular smooth muscle cells by preventing estradiol metabolism. Hypertension 51 (2008) 1197-1202
32. Dubey R.K., et al. Cytochromes 1A1/1B1-and catechol-O-methyltransferase-derived metabolites mediate estradiol-induced antimitogenesis in human cardiac fibroblast. J. Clin. Endocrinol. Metab. 90 (2005) 247-255
33. Iafrati M.D., et al. Estrogen inhibits the vascular injury response in estrogen receptor alpha-deficient mice. Nature Med. 3 (1997) 545-548
34. Karas R.H., et al. Estrogen inhibits the vascular injury response in estrogen receptor beta-deficient female mice. Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 15133-15136
35. Karas R.H., et al. Effects of estrogen on the vascular injury response in estrogen receptor alpha,beta (double) knockout mice. Circ. Res. 89 (2001) 534-539
36. Pare G., et al. Estrogen receptor-α mediates the protective effects of estrogen against vascular injury. Circ. Res. 90 (2002) 1087-1092
37. Hodgin J.B., et al. Estrogen receptor α is a major mediator of 17β-estradiol's atheroprotective effects on lesion size in Apoe-/- mice. J. Clin. Invest. 107 (2001) 333-340
38. Hodgin J.B., and Maeda N. Estrogen and mouse models of atherosclerosis. Endocrinology 143 (2002) 4495-4501
39. Zacharia L.C., et al. Methoxyestradiols mediate the antimitogenic effects of 17 beta-estradiol - Direct evidence from catechol-O-methyltransferase-knockout mice. Circulation 108 (2003) 2974-2978
40. Bakir S., et al. Estrogen-induced vasoprotection is estrogen receptor dependent - Evidence from the balloon-injured rat carotid artery model. Circulation 101 (2000) 2342-2344
41. Finking G., et al. Reduction of post injury neointima formation due to 17beta-estradiol and phytoestrogen treatment is not influenced by the pure synthetic estrogen receptor antagonist ICI 182, 780 in vitro. BMC Cardiovasc. Disord. 2 (2002) 13
42. Josefsson E., and Tarkowski A. Suppression of type II collagen-induced arthritis by the endogenous estrogen metabolite 2-methoxyestradiol. Arthritis Rheum. 40 (1997) 154-163
43. Mabjeesh N.J., et al. 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell 3 (2003) 363-375
44. Robinson M.R., et al. Safety and pharmacokinetics of intravitreal 2-methoxyestradiol implants in normal rabbit and pharmacodynamics in a rat model of choroidal neovascularization. Exp. Eye Res. 74 (2002) 309-317
45. Becker C.M., et al. 2-methoxyestradiol inhibits hypoxia-inducible factor-1 alpha and suppresses growth of lesions in a mouse model of endometriosis. American J. Pathol. 172 (2008) 534-544
46. Semenza G.L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 3 (2003) 721-732
47. Gui Y., and Zheng X.L. 2-methoxyestradiol induces cell cycle arrest and mitotic cell apoptosis in human vascular smooth muscle cells. Hypertension 47 (2006) 271-280
48. LaVallee T.M., et al. 2-methoxyestradiol up-regulates death receptor 5 and induces apoptosis through activation of the extrinsic pathway. Cancer Res. 63 (2003) 468-475
49. Kim P.K.M., et al. The role of caspase-8 in resistance to cancer chemotherapy. Drug Resist. Updates 4 (2001) 293-296
50. Chauhan D., et al. JNK-dependent release of mitochondrial protein, Smac, during apoptosis in multiple myeloma (MM) cells. J. Biol. Chem. 278 (2003) 17593-17596