Small molecule DTDQ exerts anti-metastatic effects in DU145 human castration-resistant prostate cancer cells via modulations of ERK, JNK, p38 and c-Myc signaling pathways
- Authors
- Son J.; Lee S.Y.
- Issue Date
- Jul-2020
- Publisher
- Elsevier Ltd
- Keywords
- c-Myc; Castration-resistant prostate cancer; DTDQ; MAPK; Matrix metalloproteinase
- Citation
- Bioorganic and Medicinal Chemistry Letters
- Journal Title
- Bioorganic and Medicinal Chemistry Letters
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/60122
- DOI
- 10.1016/j.bmcl.2020.127223
- ISSN
- 0960-894X
- Abstract
- Small molecule is an organic compound with low molecular mass and can be used as a drug to treat cancer cells. 6,7-dimethyl-4-(3,4,5-trimethoxyphenyl)-3,4-dihydroquinolin-2(1H)-one (DTDQ) is a small molecule known to have potential anti-metastatic effects in human non-small cell lung cancer cells. Prostate cancer is one of the most common cancers in men and can progress to metastatic castration-resistant prostate cancer (CRPC) which possesses resistance to androgen deprivation therapy. In this study, we investigated the anti-metastatic effects of DTDQ in DU145 human CRPC cells. The results showed that DTDQ inhibited proliferation, migration and invasion of DU145 human CRPC cells. DTDQ suppressed activities of MMP-2 and MMP-9 of DU145 human CRPC cells via transcriptional regulation. DTDQ modulates the three major mitogen-activated protein kinases (MAPKs), ERK, JNK and p38 that are intimately associated with cancer cell metastasis. DTDQ also down-regulates c-Myc transcription factor of DU145 CRPC cells. Finally, we observed anti-metastatic effects of DTDQ in PC3 human CRPC cells, indicating that repressive effects of DTDQ are not limited to DU145 human CRPC cells. These results suggest that DTDQ may be a potential candidate of an anti-metastatic drug to treat human CRPC. © 2020 Elsevier Ltd
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