Novel interferon-lambdas induce antiproliferative effects in neuroendocrine tumor cells

Biochem Biophys Res Commun. 2006 Jun 16;344(4):1334-41. doi: 10.1016/j.bbrc.2006.04.043. Epub 2006 Apr 24.

Abstract

Interferon-alpha (IFN-alpha) is used for biotherapy of neuroendocrine carcinomas. The interferon-lambdas (IL-28A/B and IL-29) are a novel group of interferons. In this study, we investigated the effects of the IFN-lambdas IL-28A and IL-29 on human neuroendocrine BON1 tumor cells. Similar to IFN-alpha, incubation of BON1 cells with IL-28A (10 ng/ml) and IL-29 (10 ng/ml) induced phosphorylation of STAT1, STAT2, and STAT3, significantly decreased cell numbers in a proliferation assay, and induced apoptosis as demonstrated by poly(ADP-ribose) polymerase (PARP)-cleavage, caspase-3-cleavage, and DNA-fragmentation. Stable overexpression of suppressor of cytokine signaling proteins (SOCS1 and SOCS3) completely abolished the aforementioned effects indicating that SOCS proteins act as negative regulators of IFN-lambda signaling in BON1 cells. In conclusion, the novel IFN-lambdas IL-28A and IL-29 potently induce STAT signaling and antiproliferative effects in neuroendocrine BON1 tumor cells. Thus, IFN-lambdas may hint a promising new approach in the antiproliferative therapy of neuroendocrine tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Caspase 3
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytokines / pharmacology
  • Cytokines / therapeutic use*
  • DNA Fragmentation
  • Humans
  • Interferons / pharmacology
  • Interferons / therapeutic use*
  • Interleukins / pharmacology
  • Interleukins / therapeutic use*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / metabolism
  • Phosphorylation
  • Poly(ADP-ribose) Polymerases
  • Receptors, Cytokine / metabolism
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-10
  • Repressor Proteins / metabolism
  • STAT Transcription Factors / metabolism
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / metabolism

Substances

  • Cytokines
  • interferon-lambda, human
  • Interleukins
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Cytokine
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Repressor Proteins
  • SOCS1 protein, human
  • SOCS3 protein, human
  • STAT Transcription Factors
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • interleukin 28alpha receptor
  • Interferons
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • Caspase 3
  • Caspases