Recombinant IFN-alpha2b treatment activates poly (ADPR) polymerase-1 (PARP-1) in KB cancer cells

Eur J Cancer. 2003 Sep;39(14):2103-9. doi: 10.1016/s0959-8049(03)00433-7.

Abstract

In the present paper, we investigated the relationship between the growth inhibitory effects of recombinant interferon-alpha2b (rIFN-alpha2b) and poly (ADPR) polymerase-1 (PARP-1) activity in the human squamous KB cancer cell line. Growth inhibition of the KB cells mediated by 1000 IU/ml of rIFN-alpha2b was accompanied by a transient rise in PARP-1 specific activity 24 h after rIFN-alpha2b treatment, confirmed by both the increase of intracellular poly (ADP-ribose) content and the PARP-1 auto-modification level. At longer times of incubation, the onset of apoptosis accompanied KB cell growth inhibition, as demonstrated by both flow cytometry and western-blotting analysis showing an 89 kDa apoptotic fragment of PARP-1. Moreover, pretreatment of the cells with the PARP-1 inhibitor, 3-aminobenzamide (3-ABA), at non-cytotoxic concentrations (1 mM), reduced the cell-growth inhibition, cell-cycle perturbation and apoptosis caused by rIFN-alpha2b. Taken together, these results strongly suggest that PARP-1 may be directly involved in the effects of rIFN-alpha2b in the KB cancer cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Blotting, Western
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle
  • Cell Division
  • Enzyme Activation
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • KB Cells
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Recombinant Proteins
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Poly(ADP-ribose) Polymerases