Cancer Therapy

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The antitumor activity of the fungicide ciclopirox

  1. Hongyu Zhou1,
  2. Tao Shen1,
  3. Yan Luo1,
  4. Lei Liu1,
  5. Wenxing Chen1,
  6. Baoshan Xu1,
  7. Xiuzhen Han1,
  8. Jia Pang2,
  9. Chantal A. Rivera2,
  10. Shile Huang1,3,†,*

Article first published online: 11 MAR 2010

DOI: 10.1002/ijc.25255

Issue

International Journal of Cancer

International Journal of Cancer

Volume 127, Issue 10, pages 2467–2477, 15 November 2010

Additional Information

How to Cite

Zhou, H., Shen, T., Luo, Y., Liu, L., Chen, W., Xu, B., Han, X., Pang, J., Rivera, C. A. and Huang, S. (2010), The antitumor activity of the fungicide ciclopirox. Int. J. Cancer, 127: 2467–2477. doi: 10.1002/ijc.25255

Author Information

  1. 1

    Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA

  2. 2

    Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA

  3. 3

    Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA

  1. †

    Fax: +318-675-5180

*Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA

  1. †

    Fax: +318-675-5180

Publication History

  1. Issue published online: 11 MAR 2010
  2. Article first published online: 11 MAR 2010
  3. Manuscript Accepted: 2 FEB 2010
  4. Manuscript Received: 14 JAN 2010

Funded by

  • NIH. Grant Number: CA115414
  • American Cancer Society Award. Grant Number: RSG-08-135-01-CNE
  • Louisiana State University Health Sciences Center in Shreveport, LA (Feist-Weiller Cancer Research Award and a Start-up Fund)

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Keywords:

  • ciclopirox;
  • cell proliferation;
  • cell cycle;
  • apoptosis;
  • retinoblastoma protein

Abstract

Ciclopirox olamine (CPX) is a synthetic antifungal agent clinically used to treat mycoses of the skin and nails. Here, we show that CPX inhibited tumor growth in human breast cancer MDA-MB-231 xenografts. To unveil the underlying mechanism, we further studied the antitumor activity of CPX in cell culture. The results indicate that CPX inhibited cell proliferation and induced apoptosis in human rhabdomyosarcoma (Rh30), breast carcinoma (MDA-MB231) and colon adenocarcinoma (HT-29) cells in a concentration-dependent manner. By cell cycle analysis, CPX induced accumulation of cells in G1/G0 phase of the cell cycle. Concurrently, CPX downregulated cellular protein expression of cyclins (A, B1, D1 and E) and cyclin-dependent kinases (CDK2 and CDK4) and upregulated expression of the CDK inhibitor p21Cip1, leading to hypophosphorylation of retinoblastoma protein. CPX also downregulated protein expression of Bcl-xL and survivin and enhanced cleavages of Bcl-2. Z-VAD-FMK, a pan-caspase inhibitor, partially prevented CPX-induced cell death, suggesting that CPX-induced apoptosis of cancer cells is mediated at least in part through caspase-dependent mechanism. The results indicate that CPX is a potential antitumor agent.

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