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 G(1)/G(0) 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 p21(Cip1), 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.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Zhou H,Shen T,Luo Y,Liu L,Chen W,Xu B,Han X,Pang J,Rivera CA,Huang Sdoi
10.1002/ijc.25255subject
Has Abstractpub_date
2010-11-15 00:00:00pages
2467-77issue
10eissn
0020-7136issn
1097-0215journal_volume
127pub_type
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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pub_type: 杂志文章,多中心研究
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