The Antitumor Effect of DYC-279 on Human Hepatocellular Carcinoma HepG2 Cells

Pharmacology. 2016;97(3-4):177-83. doi: 10.1159/000444174. Epub 2016 Feb 6.

Abstract

DYC-279 is a newly synthesized compound. In this study, we revealed that DYC-279 could inhibit the proliferation of HepG2 cells in a dose- and time-dependent manner using the CCK-8 test. FACS showed that DYC-279 induced a G2/M arrest and apoptosis in a dose-dependent manner. Western blot demonstrated that DYC-279-induced G2/M arrest effect was correlated with the inhibition of cyclin-dependent kinase 1 activity, including a concomitant downregulation of cyclinD1 and cdc2 and upregulation of cyclinB1 in HepG2 cells. DYC-279 also significantly increased the ratio of Bax/Bcl-2, and stimulated the released of cytochrome c into cytosol and also activated caspase-9 and caspase-3, suggesting DYC-279 induced apoptosis via mitochondrial apoptotic pathway. These data support that DYC-279 has anticancer properties in HepG2 cells and may be used as a novel effective reagent in the treatment of human liver cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • CDC2 Protein Kinase
  • Carcinoma, Hepatocellular / metabolism*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cytochromes c / metabolism
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / metabolism*
  • Piperazines / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Triazoles / pharmacology*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents
  • BAX protein, human
  • CCNB1 protein, human
  • CCND1 protein, human
  • Cyclin B1
  • DYC-279
  • Piperazines
  • Proto-Oncogene Proteins c-bcl-2
  • Triazoles
  • bcl-2-Associated X Protein
  • Cyclin D1
  • Cytochromes c
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases
  • Caspase 3
  • Caspase 9