2-methoxyestradiol inhibits hypoxia-inducible factor-1{alpha} and suppresses growth of lesions in a mouse model of endometriosis.

The American Journal of Pathology
Christian M BeckerRobert J D'Amato

Abstract

Endometriosis, the presence of ectopic endometrial tissue outside the uterine cavity, is a common disease affecting women during their reproductive years. Current therapeutic success is often unsatisfactory because of limited insight into disease mechanisms. Nevertheless, angiogenesis plays an essential role in the pathogenesis of the disease, making it a potential novel target for therapy. In the current study, we demonstrate in an established mouse model of endometriosis that transient hypoxia in transplanted endometriosis-like lesions results in the up-regulation of hypoxia-inducible factor-1alpha (HIF-1alpha), leading to the expression of vascular endothelial growth factor (VEGF), a key player in endometriosis-associated angiogenesis. Systemic treatment with the angiogenesis inhibitor 2-methoxyestradiol suppressed HIF-1alpha expression in vivo, resulting in a decreased downstream expression of HIF-1alpha target genes, such as for VEGF, phosphoglycerate kinase, and glucose transporter-1. 2-Methoxyestradiol also suppressed VEGF-induced vascular permeability, as demonstrated in a modified Miles assay. Finally, systemic treatment with 2-methoxyestradiol significantly inhibited the growth of endometriosis-like lesions in a dose-...Continue Reading

References

Jun 15, 1989·Biochemical and Biophysical Research Communications·N Ferrara, W J Henzel
Apr 1, 1981·British Journal of Cancer·J D ChapmanJ Sharplin
Oct 15, 1981·American Journal of Obstetrics and Gynecology·W P DmowskiG F Baker
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G L WangG L Semenza
May 1, 1995·Reproductive Toxicology·A M Cummings, J L Metcalf
Jan 20, 1995·The Journal of Biological Chemistry·G L Wang, G L Semenza
Jan 1, 1994·Gynecologic and Obstetric Investigation·P J van der LindenJ L Evers
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·R J D'AmatoE Hamel
May 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·G L Wang, G L Semenza
Sep 1, 1996·Molecular and Cellular Biology·J A ForsytheG L Semenza
Apr 25, 1997·The Journal of Biological Chemistry·C W PughP J Ratcliffe
Aug 4, 1998·Human Reproduction·J DonnezM Nisolle
Aug 17, 1999·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·B MeisterR Möhle
Feb 8, 2000·Biological Chemistry·P ScheideggerR Jaussi
Jul 28, 2001·Human Reproduction·R GrümmerE Winterhager
Apr 13, 2002·Annals of the New York Academy of Sciences·Kaylon L Bruner-TranKevin G Osteen
Apr 13, 2002·Annals of the New York Academy of Sciences·Robert N TaylorMichael D Mueller
Nov 21, 2002·Gynecologic and Obstetric Investigation·Jacques DonnezMieille Smets
Feb 21, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Doris MayrBirgit Anderegg
May 3, 2003·Cancer Cell·Nicola J MabjeeshParaskevi Giannakakou
May 22, 2003·The American Journal of Pathology·Harold F Dvorak
Jun 6, 2003·The Journal of Clinical Endocrinology and Metabolism·M Louise HullStephen K Smith
Mar 6, 2004·The Journal of Clinical Endocrinology and Metabolism·Annemiek W NapPatrick G Groothuis
May 12, 2004·Fertility and Sterility·UNKNOWN Practice Committee of the American Society for Reproductive Medicine
Dec 30, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Justin L RickerCarter Van Waes
Mar 16, 2005·Cancer Cell·Ronit Satchi-FainaroJudah Folkman
Jul 13, 2005·Fertility and Sterility·Johannes L H EversPatrick Groothuis
Aug 9, 2005·Fertility and Sterility·Julie EggermontAnne Van Langendonckt
Oct 8, 2005·Fertility and Sterility·Christian M BeckerRobert J D'Amato

❮ Previous
Next ❯

Citations

Mar 27, 2012·Human Reproduction·J Rudzitis-AuthM W Laschke
Dec 4, 2012·Human Reproduction·Shuang-Zheng JiaJinhua Leng
Sep 24, 2009·Human Reproduction Update·E Maria C Ohlsson TeagueM Louise Hull
May 19, 2011·Human Reproduction Update·M W LaschkeM D Menger
Jun 22, 2012·Human Reproduction Update·M W Laschke, M D Menger
Apr 24, 2008·Molecular Human Reproduction·Anne Van LangendoncktPatrick G Groothuis
Feb 4, 2009·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·Gaia GoteriAndrea Ciavattini
Apr 14, 2012·International Journal of Gynecological Pathology : Official Journal of the International Society of Gynecological Pathologists·Masafumi KatoKenichi Furuya
Jan 26, 2010·Pediatric Research·Carmen M BarnesAnne R Hansen
May 18, 2010·Virchows Archiv : an International Journal of Pathology·Gaia GoteriAndrea Ciavattini
Apr 26, 2014·Hormones & Cancer·Mauricio P PintoGareth I Owen
Jun 16, 2011·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Xiao-Yu XinSheng-Di Chen
Jan 23, 2016·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Eleftherios P SamartzisBrigitte Leeners
Dec 3, 2008·Expert Opinion on Emerging Drugs·Sun-Wei Guo
Jul 12, 2008·Expert Opinion on Investigational Drugs·Luigi FedelePaola Vigano
Jul 23, 2015·Current Eye Research·Jin-Wook JangDoo-Sik Kim
Feb 12, 2013·Climacteric : the Journal of the International Menopause Society·Z Z ZhangG P Wan
Feb 26, 2013·Journal of Reproductive Immunology·Andrew K EdwardsChandrakant Tayade
Apr 7, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Mark P Thomas, Barry V L Potter
Jun 15, 2013·Obstetrics and Gynecology International·Ana Luiza L RochaRobert N Taylor
Sep 4, 2012·Fertility and Sterility·Sérgio Reis SoaresAntonio Pellicer
May 16, 2014·Fertility and Sterility·Chin Wen TanJerry Kok Yen Chan
Apr 22, 2009·Reproductive Sciences·Sylvie DefrèreAnne Van Langendonckt
Mar 5, 2013·Reproductive Sciences·Alejandra Perez-SepulvedaSebastián E Illanes
Sep 27, 2015·Reproductive Sciences·Irene FilippiFelice Petraglia
Jul 15, 2015·Reproductive Sciences·Mahaut LeconteFrédéric Batteux
Aug 10, 2012·Reproductive Sciences·Francisco Machado-LindeJuan J Parrilla
Feb 22, 2018·International Journal of Molecular Sciences·Swati AgrawalChristian Becker
Jul 23, 2011·Gynecologic and Obstetric Investigation·S WilkoszS Herrick

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.