2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF Academic Article Article uri icon


MeSH Major

  • Financing, Organized
  • Medical Oncology
  • National Institutes of Health (U.S.)
  • Neoplasms
  • Research Support as Topic
  • Training Support


  • Inhibition of angiogenesis is an important new modality for cancer treatment. 2-methoxyestradiol (2ME2) is a novel antitumor and antiangiogenic agent, currently in clinical trials, whose molecular mechanism of action remains unclear. Herein, we report that 2ME2 inhibits tumor growth and angiogenesis at concentrations that efficiently disrupt tumor microtubules (MTs) in vivo. Mechanistically, we found that 2ME2 downregulates hypoxia-inducible factor-1 (HIF) at the posttranscriptional level and inhibits HIF-1-induced transcriptional activation of VEGF expression. Inhibition of HIF-1 occurs downstream of the 2ME2/tubulin interaction, as disruption of interphase MTs is required for HIF-alpha downregulation. These data establish 2ME2 as a small molecule inhibitor of HIF-1 and provide a mechanistic link between the disruption of the MT cytoskeleton and inhibition of angiogenesis.

publication date

  • April 2003



  • Academic Article


Digital Object Identifier (DOI)

  • 10.1016/S1535-6108(03)00077-1

PubMed ID

  • 12726862

Additional Document Info

start page

  • 363

end page

  • 75


  • 3


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