Two distinct mechanisms for inhibition of cell growth in human prostate carcinoma cells with antioxidant enzyme imbalance

Free Radic Biol Med. 1999 Jun;26(11-12):1554-68. doi: 10.1016/s0891-5849(99)00024-6.

Abstract

The purpose of the present study was to determine whether manganese superoxide dismutase (MnSOD) overexpression in DU145 human prostate carcinoma cells affected cell reduction-oxidation state (cell redox) and to correlate changes in cell redox status with cell cycle progression and plating efficiency. One MnSOD-overexpressing cell line had no change in other antioxidant enzymes (AEs) (nonadapted clone), whereas a second MnSOD-overexpressing cell line studied had an increase in catalase (CAT) activity (adapted clone). Correlation of biochemical studies with cell cycle studies suggested that heteroploidy observed in the nonadapted MnSOD-overexpressing cell line may be due to increased intracellular peroxides with resultant disruption of the microtubule network, while a decreased mitotic rate was associated with decreased ATP levels in mitosis. In contrast, the decrease in cell growth in the adapted cell line was demonstrated to be due to a decrease in plating efficiency. Our results demonstrate complex effects of AE imbalance on cell growth of DU145 prostate cancer cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Adenosine Triphosphate / metabolism
  • Antioxidants / metabolism*
  • Catalase / metabolism*
  • Cell Cycle / physiology
  • Cell Division / physiology
  • Clone Cells
  • Flow Cytometry
  • Glutathione / metabolism
  • Humans
  • Male
  • Microinjections
  • Oxidation-Reduction
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Superoxide Dismutase / metabolism*
  • Tumor Cells, Cultured

Substances

  • Antioxidants
  • Adenosine Triphosphate
  • Catalase
  • Superoxide Dismutase
  • Glutathione