摘要

In this study, the differentiation-promoting effects of terbinafine (Lamisil®, TB) were investigated in human epithelioid squamous carcinoma (A431) cells. The polyhydroxyethylmethacrylate (poly-HEMA)- and type-I collagen-coated culture plate models were adapted to harvest the TB-induced differentiated cells by agitation of the suspension medium. We demonstrated that p27/Kip1, p21/Cip1 and the keratinocyte differentiation marker, human involucrin (hINV), were induced (>25 μM) in TB-induced differentiated A431 cells. Animal studies demonstrated that administration of TB (10 mg/kg body weight) inhibited A431-xenografted tumor growth through differentiation processes as evidenced by expression of pancytokeratin in tumor tissues. Immunocytochemical staining analysis showed that p27/Kip1, but not p21/Cip1, positive-stained cells were detected in the early-differentiated cells of TB-treated tumor tissues. SP1, which regulates p27/Kip1 expression, was induced by TB (>10 μM) in A431 cells. The TB-induced promoter activity and protein expression levels of p27/Kip1 were significantly attenuated by pretreatment with mithramycin A, a SP1 specific inhibitor. We also demonstrated that TB-induced differentiated A431 cells sorted from the poly-HEMA-coated culture plates were arrested in the G1 phase. TB-induced G1 arrest in the suspension-cultured cells was attenuated by mithramycin A pretreatment. Such results suggest that SP1 plays a critical role in the p27/Kip1 gene transcriptional activation that may be subsequently involved in the TB-induced A431 cancer cell differentiation process.
原文英語
頁(從 - 到)1783-1796
頁數14
期刊Biochemical Pharmacology
75
發行號9
DOIs
出版狀態已發佈 - 五月 1 2008

指紋

terbinafine
Gene expression
Tumors
Cell Differentiation
Cells
Gene Expression
Suspensions
Tissue
Neoplasms
Differentiation Antigens
Collagen Type I
Transcriptional Activation
Animals
Genes
Chemical activation
G1 Phase
Keratinocytes
In Vitro Techniques
Squamous Cell Carcinoma
Cultured Cells

ASJC Scopus subject areas

  • Pharmacology

引用此文

@article{846062e1a8f34cd18ac42f61914187db,
title = "SP1-regulated p27/Kip1 gene expression is involved in terbinafine-induced human A431 cancer cell differentiation: An in vitro and in vivo study",
abstract = "In this study, the differentiation-promoting effects of terbinafine (Lamisil{\circledR}, TB) were investigated in human epithelioid squamous carcinoma (A431) cells. The polyhydroxyethylmethacrylate (poly-HEMA)- and type-I collagen-coated culture plate models were adapted to harvest the TB-induced differentiated cells by agitation of the suspension medium. We demonstrated that p27/Kip1, p21/Cip1 and the keratinocyte differentiation marker, human involucrin (hINV), were induced (>25 μM) in TB-induced differentiated A431 cells. Animal studies demonstrated that administration of TB (10 mg/kg body weight) inhibited A431-xenografted tumor growth through differentiation processes as evidenced by expression of pancytokeratin in tumor tissues. Immunocytochemical staining analysis showed that p27/Kip1, but not p21/Cip1, positive-stained cells were detected in the early-differentiated cells of TB-treated tumor tissues. SP1, which regulates p27/Kip1 expression, was induced by TB (>10 μM) in A431 cells. The TB-induced promoter activity and protein expression levels of p27/Kip1 were significantly attenuated by pretreatment with mithramycin A, a SP1 specific inhibitor. We also demonstrated that TB-induced differentiated A431 cells sorted from the poly-HEMA-coated culture plates were arrested in the G1 phase. TB-induced G1 arrest in the suspension-cultured cells was attenuated by mithramycin A pretreatment. Such results suggest that SP1 plays a critical role in the p27/Kip1 gene transcriptional activation that may be subsequently involved in the TB-induced A431 cancer cell differentiation process.",
keywords = "A431 cells, Differentiation, G1 cell cycle arrest, p27/Kip1, Terbinafine (Lamisil)",
author = "Huang, {Ching Shui} and Ho, {Wei Lu} and Lee, {Wen Sen} and Sheu, {Ming Thau} and Wang, {Ying Jan} and Tu, {Shih Hsin} and Chen, {Rong Jane} and Chu, {Jan Show} and Chen, {Li Ching} and Lee, {Chia Hwa} and How Tseng and Ho, {Yuan Soon} and Wu, {Chih Hsiung}",
year = "2008",
month = "5",
day = "1",
doi = "10.1016/j.bcp.2008.02.005",
language = "English",
volume = "75",
pages = "1783--1796",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "9",

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TY - JOUR

T1 - SP1-regulated p27/Kip1 gene expression is involved in terbinafine-induced human A431 cancer cell differentiation

T2 - An in vitro and in vivo study

AU - Huang, Ching Shui

AU - Ho, Wei Lu

AU - Lee, Wen Sen

AU - Sheu, Ming Thau

AU - Wang, Ying Jan

AU - Tu, Shih Hsin

AU - Chen, Rong Jane

AU - Chu, Jan Show

AU - Chen, Li Ching

AU - Lee, Chia Hwa

AU - Tseng, How

AU - Ho, Yuan Soon

AU - Wu, Chih Hsiung

PY - 2008/5/1

Y1 - 2008/5/1

N2 - In this study, the differentiation-promoting effects of terbinafine (Lamisil®, TB) were investigated in human epithelioid squamous carcinoma (A431) cells. The polyhydroxyethylmethacrylate (poly-HEMA)- and type-I collagen-coated culture plate models were adapted to harvest the TB-induced differentiated cells by agitation of the suspension medium. We demonstrated that p27/Kip1, p21/Cip1 and the keratinocyte differentiation marker, human involucrin (hINV), were induced (>25 μM) in TB-induced differentiated A431 cells. Animal studies demonstrated that administration of TB (10 mg/kg body weight) inhibited A431-xenografted tumor growth through differentiation processes as evidenced by expression of pancytokeratin in tumor tissues. Immunocytochemical staining analysis showed that p27/Kip1, but not p21/Cip1, positive-stained cells were detected in the early-differentiated cells of TB-treated tumor tissues. SP1, which regulates p27/Kip1 expression, was induced by TB (>10 μM) in A431 cells. The TB-induced promoter activity and protein expression levels of p27/Kip1 were significantly attenuated by pretreatment with mithramycin A, a SP1 specific inhibitor. We also demonstrated that TB-induced differentiated A431 cells sorted from the poly-HEMA-coated culture plates were arrested in the G1 phase. TB-induced G1 arrest in the suspension-cultured cells was attenuated by mithramycin A pretreatment. Such results suggest that SP1 plays a critical role in the p27/Kip1 gene transcriptional activation that may be subsequently involved in the TB-induced A431 cancer cell differentiation process.

AB - In this study, the differentiation-promoting effects of terbinafine (Lamisil®, TB) were investigated in human epithelioid squamous carcinoma (A431) cells. The polyhydroxyethylmethacrylate (poly-HEMA)- and type-I collagen-coated culture plate models were adapted to harvest the TB-induced differentiated cells by agitation of the suspension medium. We demonstrated that p27/Kip1, p21/Cip1 and the keratinocyte differentiation marker, human involucrin (hINV), were induced (>25 μM) in TB-induced differentiated A431 cells. Animal studies demonstrated that administration of TB (10 mg/kg body weight) inhibited A431-xenografted tumor growth through differentiation processes as evidenced by expression of pancytokeratin in tumor tissues. Immunocytochemical staining analysis showed that p27/Kip1, but not p21/Cip1, positive-stained cells were detected in the early-differentiated cells of TB-treated tumor tissues. SP1, which regulates p27/Kip1 expression, was induced by TB (>10 μM) in A431 cells. The TB-induced promoter activity and protein expression levels of p27/Kip1 were significantly attenuated by pretreatment with mithramycin A, a SP1 specific inhibitor. We also demonstrated that TB-induced differentiated A431 cells sorted from the poly-HEMA-coated culture plates were arrested in the G1 phase. TB-induced G1 arrest in the suspension-cultured cells was attenuated by mithramycin A pretreatment. Such results suggest that SP1 plays a critical role in the p27/Kip1 gene transcriptional activation that may be subsequently involved in the TB-induced A431 cancer cell differentiation process.

KW - A431 cells

KW - Differentiation

KW - G1 cell cycle arrest

KW - p27/Kip1

KW - Terbinafine (Lamisil)

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U2 - 10.1016/j.bcp.2008.02.005

DO - 10.1016/j.bcp.2008.02.005

M3 - Article

C2 - 18355800

AN - SCOPUS:41949095948

VL - 75

SP - 1783

EP - 1796

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 9

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