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Research ArticleExperimental Studies

STX140 and STX641 Cause Apoptosis via the Intrinsic Mitochondrial Pathway and Down-regulate Survivin and XIAP Expression in Ovarian and Prostate Cancer Cells

PAUL A. FOSTER, YAIK T. HO, SIMON P. NEWMAN, MATHEW P. LEESE, BARRY V.L. POTTER, MICHAEL J. REED and ATUL PUROHIT
Anticancer Research October 2009, 29 (10) 3751-3757;
PAUL A. FOSTER
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  • For correspondence: paul.foster@imperial.ac.uk
YAIK T. HO
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SIMON P. NEWMAN
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MATHEW P. LEESE
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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

Many anticancer drugs target microtubules and induce apoptosis. However, improved microtubule-targeting drugs, such as STX140 and STX641, are being developed. These compounds induce cell cycle arrest and apoptosis in a variety of tumour cells. The mechanisms that induce apoptosis and the key mediators involved are elucidated in this study. Results demonstrate that STX140 and STX641 depolarise mitochondrial bioenergetics and activate caspase 3/7 in A2780, LNCaP and MCF-7 cancer cells. Furthermore, both compounds cause a significant reduction in the expression of survivin and XIAP. This work details the temporal organisation of apoptosis induced by two microtubule disruptors and highlights the role that the down-regulation of survivin and XIAP may play in this process.

  • 2-Methoxyestradiol
  • estrogen
  • sulfamate
  • ovarian cancer
  • prostate cancer
  • breast cancer

Footnotes

  • ↵† Deceased 2009.

  • Disclosure of Conflict of Interest

    BVLP, MJR and AP are all consultants for Ipsen Ltd.

  • Received June 17, 2009.
  • Accepted July 8, 2009.
  • Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 29 (10)
Anticancer Research
Vol. 29, Issue 10
October 2009
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STX140 and STX641 Cause Apoptosis via the Intrinsic Mitochondrial Pathway and Down-regulate Survivin and XIAP Expression in Ovarian and Prostate Cancer Cells
PAUL A. FOSTER, YAIK T. HO, SIMON P. NEWMAN, MATHEW P. LEESE, BARRY V.L. POTTER, MICHAEL J. REED, ATUL PUROHIT
Anticancer Research Oct 2009, 29 (10) 3751-3757;

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STX140 and STX641 Cause Apoptosis via the Intrinsic Mitochondrial Pathway and Down-regulate Survivin and XIAP Expression in Ovarian and Prostate Cancer Cells
PAUL A. FOSTER, YAIK T. HO, SIMON P. NEWMAN, MATHEW P. LEESE, BARRY V.L. POTTER, MICHAEL J. REED, ATUL PUROHIT
Anticancer Research Oct 2009, 29 (10) 3751-3757;
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