The farnesyltransferase inhibitor, FPT inhibitor III upregulates Bax and Bcl-xs expression and induces apoptosis in human ovarian cancer cells

Int J Oncol. 1998 Jan;12(1):137-40.

Abstract

Deregulation in the ras oncogene is a common event in many types of human cancer. Our previous study clearly demonstrated that genetic alterations of ras oncogene are frequently found in human epithelial ovarian cancer. Recent reports have indicated that farnesyltransferase is involved in the regulation of post-translational modification and biological function of Ras proteins. Here, we report that a newly synthesized farnesyltransferase inhibitor, FPT inhibitor III, upregulates Bax and Bcl-xs expression and induces apoptosis in human ovarian cancer cells. This is a critical finding that farnesyltransferase inhibitors may directly activate apoptotic signaling pathways in cancer cells and may help to provide a new strategy in the treatment of human cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Alkyl and Aryl Transferases / metabolism
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Division / drug effects*
  • Chromatin / chemistry
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Farnesyltranstransferase
  • Female
  • Humans
  • Membrane Proteins / metabolism
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / pathology*
  • Polyisoprenyl Phosphates / pharmacology*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Sesquiterpenes
  • Tumor Cells, Cultured / drug effects
  • Up-Regulation
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • bcl-X Protein

Substances

  • BAK1 protein, human
  • BAX protein, human
  • BCL2L1 protein, human
  • Chromatin
  • Enzyme Inhibitors
  • Membrane Proteins
  • Polyisoprenyl Phosphates
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Sesquiterpenes
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • farnesyl pyrophosphate
  • Alkyl and Aryl Transferases
  • Farnesyltranstransferase