Combination treatment of hydrogen peroxide and X-rays induces apoptosis in human prostate cancer PC-3 cells

Int J Radiat Oncol Biol Phys. 2009 Oct 1;75(2):449-54. doi: 10.1016/j.ijrobp.2009.04.092.

Abstract

Purpose: To study the effect of hydrogen peroxide (H(2)O(2)) on radiation-induced apoptosis in human prostate cancer PC-3 cells.

Methods and materials: At 4h before the irradiation, PC-3 cells were exposed to 10mM ammonium chloride (NH(4)Cl) concentrations. Subsequently, cells were exposed to 0.1mM H(2)O(2) just before the irradiations, which were administered with 10-MV X-rays at doses of 10 Gy.

Results: The percentage of apoptotic cells at 48 h after X-irradiation alone, H(2)O(2) alone, and combined X-irradiation and H(2)O(2) was 1.85%, 4.85%, and 28.4%, respectively. With use of combined X-irradiation and H(2)O(2), production of reactive oxygen species (ROS) occurred 4h after the irradiation. This resulted in lysosomal rupturing, mitochondrial fragmentation, and the release of cytochrome c into the cytoplasm from the mitochondria. In contrast, when cells were exposed to NH(4)Cl before the X-irradiation and H(2)O(2) administration, apoptosis was almost completely suppressed, ROS production did not occur, lysosomal rupture and mitochondrial fragmentation were blocked, and cytochrome c was not released.

Conclusions: Hydrogen peroxide strongly enhanced lysosome-dependent radiation-induced apoptosis in human prostate cancer PC-3 cells. A combined use of X-rays and H(2)O(2) can also injure the mitochondrial cytoplasmic organelles and lead to the production of ROS that in and of itself might possibly induce apoptosis.

MeSH terms

  • Ammonium Chloride / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects*
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / radiation effects
  • Cytochromes c / metabolism
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • Lysosomes / drug effects
  • Lysosomes / radiation effects
  • Male
  • Mitochondria / drug effects
  • Mitochondria / radiation effects
  • Organelles / drug effects
  • Organelles / radiation effects
  • Oxidants / pharmacology*
  • Oxidative Stress
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Radiotherapy Dosage
  • Reactive Oxygen Species / metabolism

Substances

  • Oxidants
  • Reactive Oxygen Species
  • Ammonium Chloride
  • Cytochromes c
  • Hydrogen Peroxide