Intrinsic presence of poly (ADP-ribose) is significantly increased in malignant prostate compared to benign prostate cell lines

Anticancer Res. Mar-Apr 2003;23(2B):1473-8.

Abstract

Poly(ADP-ribosyl)ation plays important roles in cellular DNA repair mechanisms as well as in cellular proliferation and genomic stability. Four carcinoma cell lines, LNCaP, PC-3, C4-2 and MatLu, and one prostate epithelial cell line, PNT1A, were tested using the H10 antibody to poly(ADP-ribose) by Western blotting and FACS analysis for basal and activated (10 mM H2O2) PARP activity. In both analyses, higher levels of basal polymer were present in the LNCaP cell line than in the prostate epithelial cell line or the MatLu cell an line. LNCaP cells demonstrated greater than 90% positive analyzed cells in FACS analysis both before and after treatment with H2O2. PNT1A epithelial cells demonstrated evidence of polymer presence only after treatment with H2O2. Microsatellite instability due to increased oxidative damage in tumor cells has been proposed as a means for accumulation of genetic changes. As oxidative stress can stimulate poly(ADP-ribose) reactions, an increased presence of the polymer may indicate a high level of oxidative damage occurring in the tumor cells, contributing to higher levels of genetic instability towards progression.

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / pathology*
  • Adult
  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Blotting, Western
  • DNA Damage
  • Disease Progression
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm
  • Enzyme Activation / drug effects
  • Epithelial Cells / chemistry
  • Epithelial Cells / drug effects
  • Epithelial Cells / enzymology
  • Flow Cytometry
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Male
  • Neoplasm Proteins / metabolism
  • Oxidative Stress
  • Poly Adenosine Diphosphate Ribose / analysis*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Prostate / cytology
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / pathology*
  • Rats
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology

Substances

  • Antibiotics, Antineoplastic
  • Neoplasm Proteins
  • Poly Adenosine Diphosphate Ribose
  • Doxorubicin
  • Hydrogen Peroxide
  • Poly(ADP-ribose) Polymerases