Anti-proliferation effect of APO866 on C6 glioblastoma cells by inhibiting nicotinamide phosphoribosyltransferase

Eur J Pharmacol. 2012 Jan 15;674(2-3):163-70. doi: 10.1016/j.ejphar.2011.11.017. Epub 2011 Nov 19.


Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme in the salvaging pathway for the synthesis of nicotinamide adenine dinucleotide (NAD) that is involved in cell metabolism and proliferation. NAMPT is normally absent in astrocyte but highly expressed in glioblastoma, suggesting that it may promote cell survival through synthesizing more NAD. In this report, we evaluated the effect of APO866, a potent inhibitor of NAMPT against C6 glioblastoma. We found that APO866 inhibited the growth of C6 glioblastoma cells with IC(50) in nano-molar range. APO866 depleted intracellular NAD, caused marked inhibition of ERK activation and induced G2/M cell-cycle arrest. The effects by APO866 were abrogated by nicotinamide mononucleotide (NMN), the direct product of NAMPT. Administration of U0126, an ERK1/2 inhibitor, inhibited cell growth but displayed no synergistic effect with APO866. Taken together, our results indicated that APO866 is a potent growth inhibitor against glioblastoma through targeting NAMPT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology*
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / pathology*
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • M Phase Cell Cycle Checkpoints / drug effects
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • NAD / metabolism
  • Nicotinamide Phosphoribosyltransferase / antagonists & inhibitors*
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Piperidines / pharmacology*
  • Rats


  • Acrylamides
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide
  • Piperidines
  • NAD
  • Nicotinamide Phosphoribosyltransferase
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3