Radiation sensitizing effect of estramustine is not dependent on apoptosis

Anticancer Res. 2005 Jul-Aug;25(4):2873-8.

Abstract

Background: Estramustine is an anti-mitotic cytostatic drug that also enhances the effect of radiotherapy. The mechanism of radiosensitization is not thoroughly known. Since both radiotherapy and estramustine induce apoptosis in prostate cancer cells, we conducted an experiment to show whether radiosensitization is mediated by apoptosis.

Materials and methods: DU-145 human prostate cancer cells were xenografted to nude mice and treated with estramustine for 2 weeks and external radiation for 3 to 6 days (18 to 36 Gy). Tumor regression was measured mechanically and the rate of apoptosis defined by the amount of low molecular weight DNA fragmentation. Follow-up time was 1 to 18 days.

Results: The tumor size regressed in the group of mice receiving both radiotherapy and estramustine. Four weeks after the treatment, apoptosis was accentuated in the tumors treated with estramustine or radiation but not with their combination.

Conclusion: Estramustine potentiates radiotherapy, but not by enhancing radiation-induced apoptosis.

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Agents, Hormonal / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Combined Modality Therapy
  • DNA Fragmentation / drug effects
  • DNA Fragmentation / radiation effects
  • Estramustine / adverse effects
  • Estramustine / pharmacology*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Radiation-Sensitizing Agents / adverse effects
  • Radiation-Sensitizing Agents / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Hormonal
  • Radiation-Sensitizing Agents
  • Estramustine