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Research ArticleExperimental Studies

A New Micronized Formulation of 2-Methoxyestradiol-bis-sulfamate (STX140) is Therapeutically Potent against Breast Cancer

PAUL A. FOSTER, SIMON P. NEWMAN, MATHEW P. LEESE, SONIA BERNETIERE, CHRISTIAN DIOLEZ, JOSE CAMARA, BEATRICE HACHER, MARIE-MADELEINE BARONNET, TAUHID ALI, BARRY V.L. POTTER, MICHAEL J. REED and ATUL PUROHIT
Anticancer Research March 2008, 28 (2A) 577-581;
PAUL A. FOSTER
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  • For correspondence: paul.foster@imperial.ac.uk
SIMON P. NEWMAN
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MATHEW P. LEESE
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SONIA BERNETIERE
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CHRISTIAN DIOLEZ
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JOSE CAMARA
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BEATRICE HACHER
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MARIE-MADELEINE BARONNET
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TAUHID ALI
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BARRY V.L. POTTER
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MICHAEL J. REED
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ATUL PUROHIT
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Abstract

There is a continued need for orally bioavailable anticancer compounds that exhibit good efficacy against breast cancer. STX140, a derivative of 2-methoxyestradiol (2-MeOE2), has been shown to have excellent oral bioavailability and significantly reduces tumor growth. A new micronized formulation of STX140 has now been developed and its pharmacokinetics (PK) in rats and effect on MDA-MB-231 breast cancer growth in nude mice was investigated. Materials and Methods: For the PK studies, female Wistar rats were treated orally with STX140 in two separate vehicles (10% tetrahydrofuran (THF) in propylene glycol (PG) or 0.5% methyl cellulose (MC) in saline) and plasma samples taken for high performance liquid chromatography analysis over 48 h. For the tumor efficacy studies, female nude mice were inoculated with MDA-MB-231 breast cancer cells and then treated orally with a range of doses of STX140. Results: The PK studies demonstrated that the THF/PG vehicle resulted in a greater oral bioavailability of STX140 compared to the 0.5% MC vehicle. However, this was not translated to the tumor efficacy studies where STX140 at 20 mg/kg in either vehicle caused a significant reduction in tumor volume. Conclusion: The new micronized formulation of STX140 is orally bioavailable and efficacious at inhibiting MDA-MB-231 breast tumor growth.

  • 2-methoxyestradiol
  • estrogen
  • sulfamate
  • breast cancer
  • STX140
  • Received November 1, 2007.
  • Revision received December 27, 2007.
  • Accepted January 31, 2008.
  • Copyright© 2008 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 28 (2A)
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March-April 2008
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A New Micronized Formulation of 2-Methoxyestradiol-bis-sulfamate (STX140) is Therapeutically Potent against Breast Cancer
PAUL A. FOSTER, SIMON P. NEWMAN, MATHEW P. LEESE, SONIA BERNETIERE, CHRISTIAN DIOLEZ, JOSE CAMARA, BEATRICE HACHER, MARIE-MADELEINE BARONNET, TAUHID ALI, BARRY V.L. POTTER, MICHAEL J. REED, ATUL PUROHIT
Anticancer Research Mar 2008, 28 (2A) 577-581;

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A New Micronized Formulation of 2-Methoxyestradiol-bis-sulfamate (STX140) is Therapeutically Potent against Breast Cancer
PAUL A. FOSTER, SIMON P. NEWMAN, MATHEW P. LEESE, SONIA BERNETIERE, CHRISTIAN DIOLEZ, JOSE CAMARA, BEATRICE HACHER, MARIE-MADELEINE BARONNET, TAUHID ALI, BARRY V.L. POTTER, MICHAEL J. REED, ATUL PUROHIT
Anticancer Research Mar 2008, 28 (2A) 577-581;
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