Apoptosis-mediated cytotoxic effects of ibandronic acid on hormone- and drug-refractory prostate cancer cells and human breast cancer cells

J Int Med Res. 2010 Sep-Oct;38(5):1663-72. doi: 10.1177/147323001003800511.

Abstract

Over 80% of patients with advanced breast and prostate cancer ultimately develop bone metastases. Ibandronic acid has proven efficacy for treatment of bone metastasis secondary to breast cancer. This study was designed to investigate the cytotoxic and apoptotic effects of ibandronic acid on hormone- and drug-refractory prostate carcinoma DU-145 and human breast cancer MCF-7 cell lines. Cytotoxicity was evaluated using an XTT cell proliferation kit, and apoptosis was assessed by enzyme-linked immunosorbent assay (histone-DNA fragmentation) and measurement of caspase 3/7 activity. With increasing concentrations of ibandronic acid there was a dose- and time-dependent decrease in cell numbers. MCF-7 cells were more resistant than DU-145 cells (half maximal inhibitory concentrations of 122 and 90 microM, respectively). Ibandronic acid induced apoptosis in both cell lines. The study showed an apoptosis-mediated cytotoxic effect for ibandronic acid (in addition to the already known osteoclast inhibiting effect) in breast cancer patients with bone metastases; which was also observed in prostate cancer cells. Further clinical studies involving breast and prostate cancer patients with bone metastases are warranted to confirm these findings.

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Bone Density Conservation Agents / pharmacology
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary*
  • Bone Resorption / drug therapy
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Proliferation / drug effects
  • Diphosphonates / pharmacology*
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Humans
  • Ibandronic Acid
  • Male
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / pathology*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Caspase 3
  • Caspase 7
  • Ibandronic Acid