Cytokine induced apoptosis in human retinoblastoma cells

Mol Vis. 2004 Apr 22;10:315-22.

Abstract

Purpose: To determine potential anti-proliferative properties of interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF-alpha) on human retinoblastoma cells.

Methods: Fluorescent antibody staining was used to detect IFN-gamma and TNF-alpha receptors on the cells. Y79 and Weri Rb-1 cells were exposed to IFN-gamma alone, TNF-alpha alone, or a combination of IFN-gamma and TNF-alpha, and apoptosis was measured by caspase 3 activation and annexin V staining. Cell cycle arrest was measured by BrdU incorporation and FACS analysis.

Results: Both cell lines expressed receptors for IFN-gamma and TNF-alpha. There appeared to be two populations of both receptors in the Weri Rb-1 cell line. Apoptosis was induced in Y79 cells by IFN-gamma, but not TNF-alpha, and the combination of the cytokines did not increase apoptosis above IFN-gamma alone in Y79 cells. Apoptosis was induced in Weri Rb-1 cells only upon exposure to both cytokines. The cell cycle was not significantly altered in either cell line.

Conclusions: Human retinoblastoma cells respond to IFN-gamma or a combination of IFN-gamma and TNF-alpha by becoming apoptotic, but Y79 and Weri Rb-1 cells behave differently. The differential response of the two cell lines is not due to a lack of expression of IFN-gamma or TNF-alpha receptors. The data raise the possibility that differences in apoptotic pathways exist between the two cell lines with interesting implications for the induction of apoptosis as a therapy for retinoblastoma.

Publication types

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

MeSH terms

  • Annexin A5 / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3
  • Caspases / metabolism
  • Cell Cycle / drug effects
  • DNA Replication
  • Drug Therapy, Combination
  • Flow Cytometry
  • Humans
  • Interferon-gamma / pharmacology*
  • Receptors, Interferon / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • Retinal Neoplasms / metabolism
  • Retinal Neoplasms / pathology*
  • Retinoblastoma / metabolism
  • Retinoblastoma / pathology*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Annexin A5
  • Antineoplastic Agents
  • Receptors, Interferon
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • interferon gamma receptor
  • Interferon-gamma
  • CASP3 protein, human
  • Caspase 3
  • Caspases