2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1) induces mitotic phase arrest in A549 cells

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• 作者：Mei-Hua Hsu ; Chun-Jen Chen ; Sheng-Chu Kuo ; Jing-Gung Chung ; Ya-Yun Lai ; Che-Ming Teng ; Shiow-Lin Pan ; Li-Jiau Huang
• 关键词：2-Phenyl-4-quinolone (2-PQ) ; 2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1 ; 4-dihydroquinoline-3-carboxylic acid (YJC-1) ; Mitotic phase arrest ; Microtubule polymerization ; p21^Cip1/Waf1 ; A549 cells
• 刊名：European Journal of Pharmacology
• 出版年：2007
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：15 March 2007
• 卷：559
• 期：1
• 页码：14-20
• 文件大小：761 K

摘要

A 2-phenyl-4-quinolone (2-PQ) derivative, 2-(3-fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1), was synthesized in our laboratory. In this study, we delineated the growth-inhibitory effect of YJC-1 in human lung carcinoma A549 cells. YJC-1 inhibited cell growth with an IC₅₀ value of about 4.8 μM via microtubule polymerization, causing growth arrest in the mitotic phase. Immunoblotting analysis revealed a dramatic induction of cyclin-dependent kinase (CDK) inhibitor p21^Cip1/Waf1 and down-regulation of Cdc25C phosphatase to inhibit the protein expression of cyclin B1 and CDK1. We also found that YJC-1 induced a profound time-dependent elevation in p21^Cip1/Waf1 gene expression in comparison with the negative control. In vivo, we also found that YJC-1 significantly suppressed tumor growth in mice inoculated with A549 cells. These findings suggest that YJC-1 can suppress A549 cell growth via mitotic phase arrest.