Bisphosphonates induce apoptosis in CLL cells independently of MDR phenotype

Cancer Chemother Pharmacol. 2008 Jun;62(1):165-71. doi: 10.1007/s00280-008-0710-1. Epub 2008 Mar 12.

Abstract

Purpose: The anti-tumoral activity of bisphosphonates (BPs) has been reported in leukemia. In this study, we attempted to evaluate the apoptotic effects of the BPs pamidronate (PAM) and zoledronic acid (ZOL) in chronic lymphocytic leukemia (CLL) samples, and to correlate it with clinical parameters and multidrug resistance (MDR) phenotype (P-glycoprotein and multidrug resistance-related protein expression and/or their functional activity).

Results: Both BPs were able to induce apoptosis significantly. No correlation was observed between BP-induced apoptosis and clinical parameters or MDR phenotype.

Conclusion: Our data suggest that concurrent or sequential administration of BPs with conventional chemotherapeutic drugs may have significant therapeutic potential for CLL patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Diphosphonates / pharmacology*
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • Flow Cytometry
  • Genes, MDR / genetics*
  • Humans
  • Imidazoles / pharmacology
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Pamidronate
  • Phenotype
  • Zoledronic Acid

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid
  • Pamidronate