Mitotic arrest induced in human DU145 prostate cancer cells in response to KHC-4 treatment

Environ Toxicol. 2016 Dec;31(12):1879-1887. doi: 10.1002/tox.22189. Epub 2015 Aug 25.

Abstract

In this study, the antitumor activity of KHC-4 was analyzed using human prostate cancer (CaP) cells and the underlining anticancer mechanisms of KHC-4 were identified. KHC-4 inhibited cell proliferation and induced cytotoxicity in the castration-resistant CaP DU145 cell line. The most effective concentration of KHC-4 was 0.1 μM. Cell cycle analysis demonstrated that KHC-4 treatment caused G2/M arrest and a subsequent increase in the sub-G1 population. Furthermore, KHC-4 is up-regulated p21, p27, and p53 in a time- and concentration-dependent manner. The exposure of cells to KHC-4 induced Cdk1/cyclin B1 complex activity, which led to cell cycle arrest. Moreover, KHC-4 inhibited the activities of MMP-2 and MMP-9 to inhibit tumor cell metastasis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1879-1887, 2016.

Keywords: DU145 cells; KHC-4; antiproliferation; cell cycle arrest; cell migration; inhibition.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • Male
  • Mitosis / drug effects*
  • Morpholines / pharmacology*
  • Prostatic Neoplasms, Castration-Resistant
  • Quinolones / pharmacology*
  • Up-Regulation

Substances

  • 2'-fluoro-6-morpholinyl-2-phenyl-4-quinolone
  • Antineoplastic Agents
  • Morpholines
  • Quinolones