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The In Vitro and In Vivo Antitumor Effects of Clotrimazole on Oral Squamous Cell Carcinoma
BACKGROUND: Clotrimazole is an antifungal imidazole derivative showing anti- neoplastic effect in some tumors, but its anticancer potential is still unclear in oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate the antitumor effect of clotrimazole, and to investigate the poss...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043897/ https://www.ncbi.nlm.nih.gov/pubmed/24892421 http://dx.doi.org/10.1371/journal.pone.0098885 |
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author | Wang, Juan Jia, Lihua Kuang, Zirong Wu, Tong Hong, Yun Chen, Xiaobing Leung, W. Keung Xia, Juan Cheng, Bin |
author_facet | Wang, Juan Jia, Lihua Kuang, Zirong Wu, Tong Hong, Yun Chen, Xiaobing Leung, W. Keung Xia, Juan Cheng, Bin |
author_sort | Wang, Juan |
collection | PubMed |
description | BACKGROUND: Clotrimazole is an antifungal imidazole derivative showing anti- neoplastic effect in some tumors, but its anticancer potential is still unclear in oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate the antitumor effect of clotrimazole, and to investigate the possible mechanism of clotrimazole-mediated antitumor activity in OSCC. METHODOLOGY: In vitro experiments, the cell viability and clonogenic ability of three human OSCC cell lines CAL27, SCC25 and UM1 were detected after clotrimazole treatment by CCK8 assay and colony formation assay. Cell cycle progression and apoptosis were assessed by flow cytometry, and the involvement of several mediators of apoptosis was examined by western blot analysis. Then, the in vivo antitumor effect of clotrimazole was investigated in CAL27 xenograft model. Immunohistochemistry and western blot analysis were performed to determine the presence of apoptotic cells and the expression of Bcl-2 and Bax in tumors from mice treated with or without clotrimazole. RESULTS: Clotrimazole inhibited proliferation in all three OSCC cell lines in a dose-and time-dependent manner, and significantly reduced the colony formation of OSCC cells in vitro. Clotrimazole caused cell cycle arrest at the G(0)/G(1) phase. In addition, clotrimazole induced apoptosis in OSCC cells, and significantly down-regulated the anti-apoptotic protein Bcl-2 and up-regulated the pro-apoptotic protein Bax. Notably, clotrimazole treatment inhibited OSCC tumor growth and cell proliferation in CAL27 xenograft model. Clotrimazole also markedly reduced Bcl-2 expression and increased the protein level of Bax in tumor tissues of xenograft model. CONCLUSION: Our findings demonstrated a potent anticancer effect of clotrimazole by inducing cell cycle arrest and cellular apoptosis in OSCC. |
format | Online Article Text |
id | pubmed-4043897 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40438972014-06-09 The In Vitro and In Vivo Antitumor Effects of Clotrimazole on Oral Squamous Cell Carcinoma Wang, Juan Jia, Lihua Kuang, Zirong Wu, Tong Hong, Yun Chen, Xiaobing Leung, W. Keung Xia, Juan Cheng, Bin PLoS One Research Article BACKGROUND: Clotrimazole is an antifungal imidazole derivative showing anti- neoplastic effect in some tumors, but its anticancer potential is still unclear in oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate the antitumor effect of clotrimazole, and to investigate the possible mechanism of clotrimazole-mediated antitumor activity in OSCC. METHODOLOGY: In vitro experiments, the cell viability and clonogenic ability of three human OSCC cell lines CAL27, SCC25 and UM1 were detected after clotrimazole treatment by CCK8 assay and colony formation assay. Cell cycle progression and apoptosis were assessed by flow cytometry, and the involvement of several mediators of apoptosis was examined by western blot analysis. Then, the in vivo antitumor effect of clotrimazole was investigated in CAL27 xenograft model. Immunohistochemistry and western blot analysis were performed to determine the presence of apoptotic cells and the expression of Bcl-2 and Bax in tumors from mice treated with or without clotrimazole. RESULTS: Clotrimazole inhibited proliferation in all three OSCC cell lines in a dose-and time-dependent manner, and significantly reduced the colony formation of OSCC cells in vitro. Clotrimazole caused cell cycle arrest at the G(0)/G(1) phase. In addition, clotrimazole induced apoptosis in OSCC cells, and significantly down-regulated the anti-apoptotic protein Bcl-2 and up-regulated the pro-apoptotic protein Bax. Notably, clotrimazole treatment inhibited OSCC tumor growth and cell proliferation in CAL27 xenograft model. Clotrimazole also markedly reduced Bcl-2 expression and increased the protein level of Bax in tumor tissues of xenograft model. CONCLUSION: Our findings demonstrated a potent anticancer effect of clotrimazole by inducing cell cycle arrest and cellular apoptosis in OSCC. Public Library of Science 2014-06-03 /pmc/articles/PMC4043897/ /pubmed/24892421 http://dx.doi.org/10.1371/journal.pone.0098885 Text en © 2014 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Wang, Juan Jia, Lihua Kuang, Zirong Wu, Tong Hong, Yun Chen, Xiaobing Leung, W. Keung Xia, Juan Cheng, Bin The In Vitro and In Vivo Antitumor Effects of Clotrimazole on Oral Squamous Cell Carcinoma |
title | The In Vitro and In Vivo Antitumor Effects of Clotrimazole on Oral Squamous Cell Carcinoma |
title_full | The In Vitro and In Vivo Antitumor Effects of Clotrimazole on Oral Squamous Cell Carcinoma |
title_fullStr | The In Vitro and In Vivo Antitumor Effects of Clotrimazole on Oral Squamous Cell Carcinoma |
title_full_unstemmed | The In Vitro and In Vivo Antitumor Effects of Clotrimazole on Oral Squamous Cell Carcinoma |
title_short | The In Vitro and In Vivo Antitumor Effects of Clotrimazole on Oral Squamous Cell Carcinoma |
title_sort | in vitro and in vivo antitumor effects of clotrimazole on oral squamous cell carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4043897/ https://www.ncbi.nlm.nih.gov/pubmed/24892421 http://dx.doi.org/10.1371/journal.pone.0098885 |
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