SP1-regulated p27/Kip1 gene expression is involved in terbinafine-induced human A431 cancer cell differentiation: An in vitro and in vivo study

Ching Shui Huang, Wei Lu Ho, Wen Sen Lee, Ming Thau Sheu, Ying Jan Wang, Shih Hsin Tu, Rong Jane Chen, Jan Show Chu, Li Ching Chen, Chia Hwa Lee, How Tseng, Yuan Soon Ho, Chih Hsiung Wu

研究成果: Article同行評審

13 引文 斯高帕斯(Scopus)

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English
頁(從 - 到)1783-1796
頁數14
期刊Biochemical Pharmacology
75
發行號9
DOIs
出版狀態Published - 2008 五月 1

All Science Journal Classification (ASJC) codes

  • 生物化學
  • 藥理

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