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The in vitro and in vivo antitumor effects of clotrimazole on oral squamous cell carcinoma.

Wang J, Jia L, Kuang Z, Wu T, Hong Y, Chen X, Leung WK, Xia J, Cheng B - PLoS ONE (2014)

Bottom Line: 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.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.Our findings demonstrated a potent anticancer effect of clotrimazole by inducing cell cycle arrest and cellular apoptosis in OSCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Medicine, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.

ABSTRACT

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 G0/G1 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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Clotrimazole induces G0/G1 cell cycle arrest in OSCC cells.OSCC cells were exposed to various concentrations of clotrimazole (0, 30 and 40 µM) for 24 h. Cell cycle distributions were analyzed by flow cytometry with PI staining. *P<0.05, **P<0.01 as compared with the CAL27 control cells; # P<0.01 as compared with the SCC25 control cells; ‡P<0.01 as compared with the UM1 control cells.
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pone-0098885-g003: Clotrimazole induces G0/G1 cell cycle arrest in OSCC cells.OSCC cells were exposed to various concentrations of clotrimazole (0, 30 and 40 µM) for 24 h. Cell cycle distributions were analyzed by flow cytometry with PI staining. *P<0.05, **P<0.01 as compared with the CAL27 control cells; # P<0.01 as compared with the SCC25 control cells; ‡P<0.01 as compared with the UM1 control cells.

Mentions: The possible effect of clotrimazole on cell cycle progression in OSCC cells was assessed by flow cytometry. Cells were treated with clotrimazole (0, 30 and 40 µM) for 24 h. Clotrimazole induced cell cycle arrest in a dose-dependent manner (Fig.3, P<0.05). Clotrimazole (40 µM) treatment significantly increased the proportion of OSCC cells in the G0/G1 phase, compared to the respective control cells (92.7±1.3% vs. 77.8±0.3% in CAL27, P = 0.002; 90.9±0.5% vs. 71.7±1.3% in SCC25, P<0.001; 87.4±0.4% vs.58.4±0.3% in UM1, P<0.001, respectively). Clotrimazole (40 µM) treatment also decreased the percentage of cells in the S phase of OSCC cell lines compared to the respective control cells (6.8±1.3% vs. 14.6±0.2% in CAL27, P = 0.023; 8.8±1.1% vs. 25.8±0.9% in SCC25, P<0.001; 7.1±1.1% vs.28.7±1.6% in UM1, P = 0.046, respectively).


The in vitro and in vivo antitumor effects of clotrimazole on oral squamous cell carcinoma.

Wang J, Jia L, Kuang Z, Wu T, Hong Y, Chen X, Leung WK, Xia J, Cheng B - PLoS ONE (2014)

Clotrimazole induces G0/G1 cell cycle arrest in OSCC cells.OSCC cells were exposed to various concentrations of clotrimazole (0, 30 and 40 µM) for 24 h. Cell cycle distributions were analyzed by flow cytometry with PI staining. *P<0.05, **P<0.01 as compared with the CAL27 control cells; # P<0.01 as compared with the SCC25 control cells; ‡P<0.01 as compared with the UM1 control cells.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4043897&req=5

pone-0098885-g003: Clotrimazole induces G0/G1 cell cycle arrest in OSCC cells.OSCC cells were exposed to various concentrations of clotrimazole (0, 30 and 40 µM) for 24 h. Cell cycle distributions were analyzed by flow cytometry with PI staining. *P<0.05, **P<0.01 as compared with the CAL27 control cells; # P<0.01 as compared with the SCC25 control cells; ‡P<0.01 as compared with the UM1 control cells.
Mentions: The possible effect of clotrimazole on cell cycle progression in OSCC cells was assessed by flow cytometry. Cells were treated with clotrimazole (0, 30 and 40 µM) for 24 h. Clotrimazole induced cell cycle arrest in a dose-dependent manner (Fig.3, P<0.05). Clotrimazole (40 µM) treatment significantly increased the proportion of OSCC cells in the G0/G1 phase, compared to the respective control cells (92.7±1.3% vs. 77.8±0.3% in CAL27, P = 0.002; 90.9±0.5% vs. 71.7±1.3% in SCC25, P<0.001; 87.4±0.4% vs.58.4±0.3% in UM1, P<0.001, respectively). Clotrimazole (40 µM) treatment also decreased the percentage of cells in the S phase of OSCC cell lines compared to the respective control cells (6.8±1.3% vs. 14.6±0.2% in CAL27, P = 0.023; 8.8±1.1% vs. 25.8±0.9% in SCC25, P<0.001; 7.1±1.1% vs.28.7±1.6% in UM1, P = 0.046, respectively).

Bottom Line: 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.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.Our findings demonstrated a potent anticancer effect of clotrimazole by inducing cell cycle arrest and cellular apoptosis in OSCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Medicine, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.

ABSTRACT

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 G0/G1 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.

Show MeSH
Related in: MedlinePlus