摘要

Terbinafine (TB) (Lamisil®), a promising oral antifungal agent used worldwide, has been used in the treatment of superficial mycosis. In our study, we demonstrated that TB dose-dependently decreased cell number in various cultured human malignant cells. Flow cytometry analysis revealed that TB interrupts the cell cycle at the G0/G1 transition. The TB-induced cell cycle arrest in colon cancer cell line (COLO 205) occurred when the cyclin-dependent kinase (cdk) system was inhibited just as the levels of p53, p21/Cip1 and p27/Kip 1 proteins were augmented. In the TB-treated COLO 205, the binding between p53 protein and p53 consensus binding site in p21/Cip1 promoter DNA probe was increased. Pretreatment of COLO 205 with p53-specific antisense oligodeoxynucleotide decreased the TB-induced elevations of p53 and p21/Cip1 proteins, which in turn led to arrest in the cell cycle at the G0/G1 phase. Moreover, in the p53 null cells, HL60, TB treatment did not induce cell cycle arrest. Taken together, these results suggest an involvement of the p53-associated signaling pathway in the TB-induced antiproliferation in COLO 205. We further examined whether administration of TB could affect the growth of tumors derived from human colon cancer cells in an in vivo setting. COLO 205 cells implanted subcutaneously in nude mice formed solid tumor; subsequent intraperitoneal injections of TB (50 mg/kg) led to obvious decline in tumor size, up to 50-60%. In these tumors, increases in the p21/Cip1, p27/Kip 1 and p53 proteins and the occurrence of apoptosis were observed. Combined treatment with TB and nocodazole (ND), a clinically used anticancer agent, potentiated the apoptotic effect in COLO 205. These findings demonstrate for the first time that TB can inhibit the proliferation of tumor cells in vitro and in vivo.
原文英語
頁(從 - 到)125-137
頁數13
期刊International Journal of Cancer
106
發行號1
DOIs
出版狀態已發佈 - 八月 10 2003

指紋

terbinafine
Cell Cycle Checkpoints
Cell Line
Neoplasms
In Vitro Techniques
Colonic Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

引用此文

In vitro and in vivo studies of the anticancer action of terbinafine in human cancer cell lines : G0/G1 p53-associated cell cycle arrest. / Lee, Wen Sen; Chen, Rong Jane; Wang, Ying Jan; Tseng, How; Jeng, Jiiang Huei; Lin, Shyr Yi; Liang, Yu Chih; Chen, Chien Ho; Lin, Chien Huang; Lin, Jen Kun; Ho, Pei Yin; Chu, Jan Show; Ho, Wei Lu; Chen, Li Ching; Ho, Yuan Soon.

於: International Journal of Cancer, 卷 106, 編號 1, 10.08.2003, p. 125-137.

研究成果: 雜誌貢獻文章

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abstract = "Terbinafine (TB) (Lamisil{\circledR}), a promising oral antifungal agent used worldwide, has been used in the treatment of superficial mycosis. In our study, we demonstrated that TB dose-dependently decreased cell number in various cultured human malignant cells. Flow cytometry analysis revealed that TB interrupts the cell cycle at the G0/G1 transition. The TB-induced cell cycle arrest in colon cancer cell line (COLO 205) occurred when the cyclin-dependent kinase (cdk) system was inhibited just as the levels of p53, p21/Cip1 and p27/Kip 1 proteins were augmented. In the TB-treated COLO 205, the binding between p53 protein and p53 consensus binding site in p21/Cip1 promoter DNA probe was increased. Pretreatment of COLO 205 with p53-specific antisense oligodeoxynucleotide decreased the TB-induced elevations of p53 and p21/Cip1 proteins, which in turn led to arrest in the cell cycle at the G0/G1 phase. Moreover, in the p53 null cells, HL60, TB treatment did not induce cell cycle arrest. Taken together, these results suggest an involvement of the p53-associated signaling pathway in the TB-induced antiproliferation in COLO 205. We further examined whether administration of TB could affect the growth of tumors derived from human colon cancer cells in an in vivo setting. COLO 205 cells implanted subcutaneously in nude mice formed solid tumor; subsequent intraperitoneal injections of TB (50 mg/kg) led to obvious decline in tumor size, up to 50-60{\%}. In these tumors, increases in the p21/Cip1, p27/Kip 1 and p53 proteins and the occurrence of apoptosis were observed. Combined treatment with TB and nocodazole (ND), a clinically used anticancer agent, potentiated the apoptotic effect in COLO 205. These findings demonstrate for the first time that TB can inhibit the proliferation of tumor cells in vitro and in vivo.",
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T2 - G0/G1 p53-associated cell cycle arrest

AU - Lee, Wen Sen

AU - Chen, Rong Jane

AU - Wang, Ying Jan

AU - Tseng, How

AU - Jeng, Jiiang Huei

AU - Lin, Shyr Yi

AU - Liang, Yu Chih

AU - Chen, Chien Ho

AU - Lin, Chien Huang

AU - Lin, Jen Kun

AU - Ho, Pei Yin

AU - Chu, Jan Show

AU - Ho, Wei Lu

AU - Chen, Li Ching

AU - Ho, Yuan Soon

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N2 - Terbinafine (TB) (Lamisil®), a promising oral antifungal agent used worldwide, has been used in the treatment of superficial mycosis. In our study, we demonstrated that TB dose-dependently decreased cell number in various cultured human malignant cells. Flow cytometry analysis revealed that TB interrupts the cell cycle at the G0/G1 transition. The TB-induced cell cycle arrest in colon cancer cell line (COLO 205) occurred when the cyclin-dependent kinase (cdk) system was inhibited just as the levels of p53, p21/Cip1 and p27/Kip 1 proteins were augmented. In the TB-treated COLO 205, the binding between p53 protein and p53 consensus binding site in p21/Cip1 promoter DNA probe was increased. Pretreatment of COLO 205 with p53-specific antisense oligodeoxynucleotide decreased the TB-induced elevations of p53 and p21/Cip1 proteins, which in turn led to arrest in the cell cycle at the G0/G1 phase. Moreover, in the p53 null cells, HL60, TB treatment did not induce cell cycle arrest. Taken together, these results suggest an involvement of the p53-associated signaling pathway in the TB-induced antiproliferation in COLO 205. We further examined whether administration of TB could affect the growth of tumors derived from human colon cancer cells in an in vivo setting. COLO 205 cells implanted subcutaneously in nude mice formed solid tumor; subsequent intraperitoneal injections of TB (50 mg/kg) led to obvious decline in tumor size, up to 50-60%. In these tumors, increases in the p21/Cip1, p27/Kip 1 and p53 proteins and the occurrence of apoptosis were observed. Combined treatment with TB and nocodazole (ND), a clinically used anticancer agent, potentiated the apoptotic effect in COLO 205. These findings demonstrate for the first time that TB can inhibit the proliferation of tumor cells in vitro and in vivo.

AB - Terbinafine (TB) (Lamisil®), a promising oral antifungal agent used worldwide, has been used in the treatment of superficial mycosis. In our study, we demonstrated that TB dose-dependently decreased cell number in various cultured human malignant cells. Flow cytometry analysis revealed that TB interrupts the cell cycle at the G0/G1 transition. The TB-induced cell cycle arrest in colon cancer cell line (COLO 205) occurred when the cyclin-dependent kinase (cdk) system was inhibited just as the levels of p53, p21/Cip1 and p27/Kip 1 proteins were augmented. In the TB-treated COLO 205, the binding between p53 protein and p53 consensus binding site in p21/Cip1 promoter DNA probe was increased. Pretreatment of COLO 205 with p53-specific antisense oligodeoxynucleotide decreased the TB-induced elevations of p53 and p21/Cip1 proteins, which in turn led to arrest in the cell cycle at the G0/G1 phase. Moreover, in the p53 null cells, HL60, TB treatment did not induce cell cycle arrest. Taken together, these results suggest an involvement of the p53-associated signaling pathway in the TB-induced antiproliferation in COLO 205. We further examined whether administration of TB could affect the growth of tumors derived from human colon cancer cells in an in vivo setting. COLO 205 cells implanted subcutaneously in nude mice formed solid tumor; subsequent intraperitoneal injections of TB (50 mg/kg) led to obvious decline in tumor size, up to 50-60%. In these tumors, increases in the p21/Cip1, p27/Kip 1 and p53 proteins and the occurrence of apoptosis were observed. Combined treatment with TB and nocodazole (ND), a clinically used anticancer agent, potentiated the apoptotic effect in COLO 205. These findings demonstrate for the first time that TB can inhibit the proliferation of tumor cells in vitro and in vivo.

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KW - Immunohistochemistry

KW - Nude mice

KW - Terbinafine (Lamisil®)

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