The antitumor activity of the fungicide ciclopirox

Authors

  • Hongyu Zhou,

    1. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA
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  • Tao Shen,

    1. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA
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  • Yan Luo,

    1. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA
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  • Lei Liu,

    1. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA
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  • Wenxing Chen,

    1. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA
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  • Baoshan Xu,

    1. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA
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  • Xiuzhen Han,

    1. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA
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  • Jia Pang,

    1. Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA
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  • Chantal A. Rivera,

    1. Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA
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  • Shile Huang

    Corresponding author
    1. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA
    2. Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA
    • Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA
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    • Fax: +318-675-5180


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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