Antitumor effects of miconazole on human colon carcinoma xenografts in nude mice through induction of apoptosis and G0/G1 cell cycle arrest

Chih Hsiung Wu, Jiiang Huei Jeng, Ying-Jan Wang, Chia Jen Tseng, Yu Chih Liang, Chien Ho Chen, Horng Mo Lee, Jen Kun Lin, Chien Huang Lin, Shyr Yi Lin, Chung Pei Li, Yuan Soon Ho

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Abstract

Miconazole (MIC), a promising oral antifungal agent, has been used worldwide in the treatment of superficial mycosis. In this study, we demonstrated that MIC dose dependently arrested various human cancer cells at the G0/G1 phase of the cell cycle. The protein levels of p53, p21/Cip1, and p27/Kip1 were significantly elevated by MIC treatment in COLO 205 cells. Electrophoretic mobility gel shift assays showed that the nuclear extracts of the MIC-treated COLO 205 cells exerted a significant binding between wild-type p53 and its consensus-binding site present in the p21/Cip1 promoter. These results suggested that the p53-associated signaling pathway is involved in the regulation of MIC-induced cancer cell growth arrest. By immunoblot analysis, we demonstrated that cyclin D3 and cyclin-dependent kinase-4 (CDK4) protein levels were inhibited by MIC treatment in the cancer cells. Significant therapeutic effect was further demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with MIC (50 mg/kg ip). The protein expression of p53 was significantly increased in MIC-treated tumor tissues by immunohistochemical staining and Western blotting analysis. DNA fragmentation and TUNEL assay were performed and demonstrated that apoptosis occurred in tumor tissues treated with MIC. Our study provides the novel mechanisms of antitumor effects of MIC and such results may have significant applications for cancer chemotherapy.

Original languageEnglish
Pages (from-to)22-35
Number of pages14
JournalToxicology and Applied Pharmacology
Volume180
Issue number1
DOIs
Publication statusPublished - 2002 Apr 1

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G1 Phase Cell Cycle Checkpoints
Miconazole
Heterografts
Nude Mice
Colon
Cells
Apoptosis
Carcinoma
Neoplasms
Tumors
Assays
Bearings (structural)
Cyclin D3
Cyclin-Dependent Kinase 4
Tissue
Electrophoretic mobility
Cell Cycle Resting Phase
Proteins
Chemotherapy
Mycoses

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

Wu, Chih Hsiung ; Jeng, Jiiang Huei ; Wang, Ying-Jan ; Tseng, Chia Jen ; Liang, Yu Chih ; Chen, Chien Ho ; Lee, Horng Mo ; Lin, Jen Kun ; Lin, Chien Huang ; Lin, Shyr Yi ; Li, Chung Pei ; Ho, Yuan Soon. / Antitumor effects of miconazole on human colon carcinoma xenografts in nude mice through induction of apoptosis and G0/G1 cell cycle arrest. In: Toxicology and Applied Pharmacology. 2002 ; Vol. 180, No. 1. pp. 22-35.
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abstract = "Miconazole (MIC), a promising oral antifungal agent, has been used worldwide in the treatment of superficial mycosis. In this study, we demonstrated that MIC dose dependently arrested various human cancer cells at the G0/G1 phase of the cell cycle. The protein levels of p53, p21/Cip1, and p27/Kip1 were significantly elevated by MIC treatment in COLO 205 cells. Electrophoretic mobility gel shift assays showed that the nuclear extracts of the MIC-treated COLO 205 cells exerted a significant binding between wild-type p53 and its consensus-binding site present in the p21/Cip1 promoter. These results suggested that the p53-associated signaling pathway is involved in the regulation of MIC-induced cancer cell growth arrest. By immunoblot analysis, we demonstrated that cyclin D3 and cyclin-dependent kinase-4 (CDK4) protein levels were inhibited by MIC treatment in the cancer cells. Significant therapeutic effect was further demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with MIC (50 mg/kg ip). The protein expression of p53 was significantly increased in MIC-treated tumor tissues by immunohistochemical staining and Western blotting analysis. DNA fragmentation and TUNEL assay were performed and demonstrated that apoptosis occurred in tumor tissues treated with MIC. Our study provides the novel mechanisms of antitumor effects of MIC and such results may have significant applications for cancer chemotherapy.",
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Antitumor effects of miconazole on human colon carcinoma xenografts in nude mice through induction of apoptosis and G0/G1 cell cycle arrest. / Wu, Chih Hsiung; Jeng, Jiiang Huei; Wang, Ying-Jan; Tseng, Chia Jen; Liang, Yu Chih; Chen, Chien Ho; Lee, Horng Mo; Lin, Jen Kun; Lin, Chien Huang; Lin, Shyr Yi; Li, Chung Pei; Ho, Yuan Soon.

In: Toxicology and Applied Pharmacology, Vol. 180, No. 1, 01.04.2002, p. 22-35.

Research output: Contribution to journalArticle

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AU - Wu, Chih Hsiung

AU - Jeng, Jiiang Huei

AU - Wang, Ying-Jan

AU - Tseng, Chia Jen

AU - Liang, Yu Chih

AU - Chen, Chien Ho

AU - Lee, Horng Mo

AU - Lin, Jen Kun

AU - Lin, Chien Huang

AU - Lin, Shyr Yi

AU - Li, Chung Pei

AU - Ho, Yuan Soon

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