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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...

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Autores principales: Wang, Juan, Jia, Lihua, Kuang, Zirong, Wu, Tong, Hong, Yun, Chen, Xiaobing, Leung, W. Keung, Xia, Juan, Cheng, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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.
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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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