Farnesyltransferase inhibitors: molecular evidence of therapeutic efficacy in acute lymphoblastic leukemia through cyclin D1 inhibition

Anticancer Res. 2012 Mar;32(3):831-8.

Abstract

Background: Farnesyltransferase inhibitors have the ability to interfere with various intracellular pathways, reducing cell survival and proliferation. They have become an attractive tool for cancer therapy, namely acute leukemias. In this work, we have studied the efficacy of α-hydroxyfarnesylphosphonic acid (α-HFPA) in CEM (acute T-cell lymphoblastic leukemia) in culture.

Materials and methods: CEM cells were incubated with α-HFPA at different concentrations; viability and proliferation studies were performed using the trypan blue exclusion assay and cell morphological analysis. Expression of lamin A/C, cyclin D1 and BAD were analyzed by flow cytometry.

Results: Our results show that α-HFPA significantly decreases Farnesyltransferase activity, reduces cell proliferation and induces cell death through apoptosis in CEM cells, which is correlated with a reduction of cyclin D1 levels.

Conclusion: This study suggests that α-HFPA blocks the cell cycle and induces cell death through apoptosis in CEM cells and may be a therapeutic approach in ALL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cyclin D1 / antagonists & inhibitors*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Farnesol / analogs & derivatives*
  • Farnesol / pharmacology
  • Farnesyltranstransferase / antagonists & inhibitors*
  • Humans
  • Organophosphonates / pharmacology*
  • Phosphorous Acids
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology

Substances

  • (alpha-hydroxyfarnesyl)phosphonic acid
  • Enzyme Inhibitors
  • Organophosphonates
  • Phosphorous Acids
  • Cyclin D1
  • Farnesol
  • Farnesyltranstransferase