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

Bioorg Med Chem Lett. 2020 Jul 1;30(13):127223. doi: 10.1016/j.bmcl.2020.127223. Epub 2020 Apr 27.

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.

Keywords: Castration-resistant prostate cancer; DTDQ; MAPK; Matrix metalloproteinase; c-Myc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Prostatic Neoplasms / drug therapy
  • Quinolones / pharmacology*

Substances

  • Antineoplastic Agents
  • Quinolones
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9