We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
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, Soonchan; Lee, Jongsung; Lee, Sang Yeol
- 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(1<italic>H</italic>)-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(1<italic>H</italic>)-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(1<italic>H</italic>)-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(1<italic>H</italic>)-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(1<italic>H</italic>)-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(1<italic>H</italic>)-one are due to sequential inactivation of the extracellular signal-regulated kinases and p38 signaling pathways.
- Subjects
NON-small-cell lung carcinoma; CANCER cells; PROTEIN kinases; DEHYDROGENASES; MITOGEN-activated protein kinases
- Publication
Cell Biochemistry & Biophysics, 2018, Vol 76, Issue 1/2, p255
- ISSN
1085-9195
- Publication type
Article
- DOI
10.1007/s12013-017-0789-2