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

doi:10.1016/j.ejphar.2006.12.001

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 journal › Article › peer-review

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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 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.

Original language	English
Pages (from-to)	14-20
Number of pages	7
Journal	European Journal of Pharmacology
Volume	559
Issue number	1
DOIs	https://doi.org/10.1016/j.ejphar.2006.12.001
Publication status	Published - Mar 15 2007

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

Pharmacology

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10.1016/j.ejphar.2006.12.001

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@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}",

note = "Funding Information: The investigation was supported by research grants from the National Science Council of the Republic of China (NSC92-2323-B-039-001 and NSC95-2320-B-039-011-MY3) awarded to S.C. Kuo and L.J. Huang.",

year = "2007",

month = mar,

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

N1 - Funding Information: The investigation was supported by research grants from the National Science Council of the Republic of China (NSC92-2323-B-039-001 and NSC95-2320-B-039-011-MY3) awarded to S.C. Kuo and L.J. Huang.

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

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U2 - 10.1016/j.ejphar.2006.12.001

DO - 10.1016/j.ejphar.2006.12.001

M3 - Article

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AN - SCOPUS:33847187394

SN - 0014-2999

VL - 559

SP - 14

EP - 20

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

IS - 1

ER -

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

Abstract

Keywords

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