2-Methoxyestradiol inhibits experimental autoimmune encephalomyelitis through suppression of immune cell activation

Gordon S. Duncan, Dirk Brenner, Michael W. Tusche, Anne Brus̈tle, Christiane B. Knobbe, Andrew J. Elia, Thomas Mock, Mark R. Bray, Peter H. Krammer, Tak W. Mak*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

42 Citations (Scopus)


The endogenous metabolite of estradiol, 2-Methoxyestradiol (2ME2), is an antimitotic and antiangiogenic cancer drug candidate that also exhibits disease-modifying activity in animal models of rheumatoid arthritis (RA). We found that 2ME2 dramatically suppresses development of mouse experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis (MS). 2ME2 inhibits in vitro lymphocyte activation, cytokine production, and proliferation in a dose-dependent fashion. 2ME2 treatment of lymphocytes specifically reduced the nuclear translocation and transcriptional activity of nuclear factor of activated T-cells (NFAT) c1, whereas NF-κB and activator protein 1 (AP-1) activation were not adversely affected.Wetherefore propose that2ME2 attenuates EAE through disruption of the NFAT pathway and subsequent lymphocyte activation. By extension, our findings provide a molecular rationale for the use of 2ME2 as a tolerable oral immunomodulatory agent for the treatment of autoimmune disorders such as MS in humans.

Original languageEnglish
Pages (from-to)21034-21039
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number51
Publication statusPublished - 18 Dec 2012
Externally publishedYes


  • Autoimmunity
  • Calcium signaling


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