Affordable Access

deepdyve-link
Publisher Website

IDH-Inhibiting Small Molecule DTDQ Inhibits Migration and Invasion of A549 Human Non-Small-Cell Lung Cancer Cells via Sequential Inactivation Of ERK and P38 Signaling Pathways.

Authors
  • Park, Soonchan1
  • Lee, Jongsung2
  • Lee, Sang Yeol3
  • 1 Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam, 461-701, South Korea. , (North Korea)
  • 2 Department of Genetic Engineering, Sungkyunkwan University, Suwon, Gyeonggi, 440-746, South Korea. , (North Korea)
  • 3 Department of Life Science, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam, 461-701, South Korea. [email protected] , (North Korea)
Type
Published Article
Journal
Cell Biochemistry and Biophysics
Publisher
Springer-Verlag
Publication Date
Mar 21, 2017
Identifiers
DOI: 10.1007/s12013-017-0789-2
PMID: 28321613
Source
Medline
Keywords
License
Unknown

Abstract

Migration and invasion are two core processes during cancer metastasis, and several signaling pathways have been shown to be involved. A key regulator of metastasis is the mitogen-activated protein kinase signaling pathway. Here, we report that the small molecule, 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one, inhibited isocitrate dehydrogenase activity and had anti-metastatic effects in A549 human non-small-cell lung cancer cells. 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one induced sequential inactivation of the extracellular signal-regulated kinases and p38 signaling pathways, both representative mitogen-activated protein kinase family members. We also found that 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one suppressed the transcription factor c-Myc, a regulator of cancer metastasis. This led to selective attenuation of matrix metalloproteinase-2 and subsequent suppression of migration and invasion in A549 non-small-cell lung cancer cells. 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one also suppressed metastasis in H1299 non-small-cell lung cancer cells, suggesting that the effects of 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one are not limited to A549 non-small-cell lung cancer cells. We therefore propose that the antimetastatic effects of 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one are due to sequential inactivation of the extracellular signal-regulated kinases and p38 signaling pathways.

Report this publication

Statistics

Seen <100 times