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Colchicine and 2-methoxyestradiol Inhibit Human Angiogenesis.

S J Stafford1, J Schwimer, C T Anthony

  • 1Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.

The Journal of Surgical Research
|April 20, 2005
PubMed
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Tubulin inhibitors like colchicine and 2-methoxyestradiol (2 MeOH) were tested for their anti-angiogenic effects. 2 MeOH showed promise for treating angiogenesis-dependent diseases due to achievable clinical plasma levels.

Area of Science:

  • Oncology
  • Vascular Biology
  • Pharmacology

Background:

  • Angiogenesis is crucial for tumor growth and metastasis.
  • Tubulin inhibitors are known to effectively inhibit angiogenesis.
  • Colchicine and 2-methoxyestradiol (2 MeOH) are tubulin inhibitors with potential anti-angiogenic properties.

Purpose of the Study:

  • To investigate the dose-dependent effects of colchicine and 2 MeOH on human angiogenic responses.
  • To determine if these tubulin inhibitors can limit neovessel growth.
  • To assess the clinical potential of 2 MeOH in treating angiogenesis-dependent diseases.

Main Methods:

  • Human placental vein discs were cultured in a fibrin-thrombin clot model.
  • Colchicine and 2 MeOH were tested across concentrations from 10(-6) to 10(-12) M.

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  • Assessed were the percentage of wells initiating angiogenesis (%I) and the angiogenic index of neovessel growth.

    • Main Results:

    • Colchicine (10(-6) and 10(-8) M) completely inhibited angiogenesis, but lower doses were ineffective.
    • Effective in vitro colchicine levels exceed achievable non-toxic human plasma levels.
    • 2-methoxyestradiol (2 MeOH) significantly inhibited angiogenesis at 10(-6) M, with achievable and non-toxic clinical plasma levels.
    • Lower doses of 2 MeOH did not significantly inhibit angiogenesis.

    Conclusions:

    • 2-methoxyestradiol (2 MeOH) demonstrates significant anti-angiogenic effects in vitro.
    • Achievable in vivo drug levels of 2 MeOH suggest its potential clinical utility.
    • 2 MeOH may be a viable therapeutic agent for angiogenesis-dependent diseases.