2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC-1) induces mitotic phase arrest in A549 cells.
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 IC(50) value of about 4.8 microM 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.
Hsu
Mei-Hua
MH
Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40421, Taiwan (ROC).
Chen
Chun-Jen
CJ
Kuo
Sheng-Chu
SC
Chung
Jing-Gung
JG
Lai
Ya-Yun
YY
Teng
Che-Ming
CM
Pan
Shiow-Lin
SL
Huang
Li-Jiau
LJ
D050256:Antimitotic Agents; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays
D050256:Antimitotic Agents; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21