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

Mei Hua Hsu, Chun Jen Chen, Sheng Chu Kuo, Jing Gung Chung, Ya Yun Lai, Che Ming Teng, Shiow Lin Pan, Li Jiau Huang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 p21Cip1/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 p21Cip1/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.

Original languageEnglish
Pages (from-to)14-20
Number of pages7
JournalEuropean Journal of Pharmacology
Volume559
Issue number1
DOIs
Publication statusPublished - Mar 15 2007
Externally publishedYes

Fingerprint

Carboxylic Acids
Growth
cdc25 Phosphatases
Cyclin B1
Cyclin-Dependent Kinases
Immunoblotting
Microtubules
Polymerization
Inhibitory Concentration 50
Down-Regulation
A549 Cells
1,4-dihydroquinoline
Carcinoma
Gene Expression
Lung
Neoplasms
Proteins

Keywords

  • 2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1)
  • 2-Phenyl-4-quinolone (2-PQ)
  • A549 cells
  • Microtubule polymerization
  • Mitotic phase arrest
  • p21

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1) induces mitotic phase arrest in A549 cells. / Hsu, Mei Hua; Chen, Chun Jen; Kuo, Sheng Chu; Chung, Jing Gung; Lai, Ya Yun; Teng, Che Ming; Pan, Shiow Lin; Huang, Li Jiau.

In: European Journal of Pharmacology, Vol. 559, No. 1, 15.03.2007, p. 14-20.

Research output: Contribution to journalArticle

Hsu, Mei Hua ; Chen, Chun Jen ; Kuo, Sheng Chu ; Chung, Jing Gung ; Lai, Ya Yun ; Teng, Che Ming ; Pan, Shiow Lin ; Huang, Li Jiau. / 2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1) induces mitotic phase arrest in A549 cells. In: European Journal of Pharmacology. 2007 ; Vol. 559, No. 1. pp. 14-20.
@article{4acc0b991a074fd29af274928a0578d2,
title = "2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1) induces mitotic phase arrest in A549 cells",
abstract = "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 p21Cip1/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 p21Cip1/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.",
keywords = "2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1), 2-Phenyl-4-quinolone (2-PQ), A549 cells, Microtubule polymerization, Mitotic phase arrest, p21",
author = "Hsu, {Mei Hua} and Chen, {Chun Jen} and Kuo, {Sheng Chu} and Chung, {Jing Gung} and Lai, {Ya Yun} and Teng, {Che Ming} and Pan, {Shiow Lin} and Huang, {Li Jiau}",
year = "2007",
month = "3",
day = "15",
doi = "10.1016/j.ejphar.2006.12.001",
language = "English",
volume = "559",
pages = "14--20",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - 2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1) induces mitotic phase arrest in A549 cells

AU - Hsu, Mei Hua

AU - Chen, Chun Jen

AU - Kuo, Sheng Chu

AU - Chung, Jing Gung

AU - Lai, Ya Yun

AU - Teng, Che Ming

AU - Pan, Shiow Lin

AU - Huang, Li Jiau

PY - 2007/3/15

Y1 - 2007/3/15

N2 - 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 p21Cip1/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 p21Cip1/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.

AB - 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 p21Cip1/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 p21Cip1/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.

KW - 2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1)

KW - 2-Phenyl-4-quinolone (2-PQ)

KW - A549 cells

KW - Microtubule polymerization

KW - Mitotic phase arrest

KW - p21

UR - http://www.scopus.com/inward/record.url?scp=33847187394&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847187394&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2006.12.001

DO - 10.1016/j.ejphar.2006.12.001

M3 - Article

VL - 559

SP - 14

EP - 20

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1

ER -