The mechanistic antitumor study of myricanol 5-fluorobenzyloxy ether in human leukemic cell HL-60

Future Med Chem. 2017 Dec;9(18):2117-2127. doi: 10.4155/fmc-2017-0165. Epub 2017 Aug 18.

Abstract

Aim: The aim of the study was to explore the growth inhibitory effect of myricanol 5-fluorobenzyloxy ether (5FEM) and the underlying mechanism in human leukemic cells HL-60.

Materials & methods: 5FEM was obtained by chemical modification of myricanol with fluorobenzyloxy ether at the OH(5) position. The cytotoxicity, cell apoptosis, cell cycle and the expression of key apoptosis-related genes in HL-60 were evaluated.

Results & conclusion: 5FEM can significantly inhibited growth of HL-60 cells, increased the G2/M population and upregulated the expression of Bax, Fas, FasL, caspase-9 and p21 and downregulated that of Bcl-2 and survivin. The results enhance our understanding of 5FEM and aid the discovery of novel myricanol derivatives as potential antitumor agents.

Keywords: antitumor; apoptosis; cell cycle; cell growth inhibition; myricanol 5-fluorobenzyloxy ether.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Caspase 9 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Diarylheptanoids / chemical synthesis
  • Diarylheptanoids / chemistry*
  • Diarylheptanoids / toxicity
  • Down-Regulation / drug effects
  • Ether / chemical synthesis
  • Ether / chemistry*
  • Ether / pharmacology
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / metabolism
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • HL-60 Cells
  • Humans
  • Leukemia
  • M Phase Cell Cycle Checkpoints / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Up-Regulation / drug effects
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • fas Receptor / genetics
  • fas Receptor / metabolism

Substances

  • Antineoplastic Agents
  • Cyclin-Dependent Kinase Inhibitor p21
  • Diarylheptanoids
  • FAS protein, human
  • Fas Ligand Protein
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • fas Receptor
  • myricanol 5-fluorobenzyloxy ether
  • Ether
  • myricanol
  • Caspase 9