Competitive inhibition by NAG-1/GDF-15 NLS peptide enhances its anti-cancer activity

Biochem Biophys Res Commun. 2019 Oct 29;519(1):29-34. doi: 10.1016/j.bbrc.2019.08.090. Epub 2019 Aug 29.

Abstract

Non-steroidal anti-inflammatory drug activated gene-1 (NAG-1), also known as growth differentiation factor 15 (GDF15), is a TGF-β (transforming growth factor beta) superfamily protein with a distinctive secretion pathway. NAG-1 is associated with multiple diseases including cancer, wherein it plays a role in both pro- and anti-cancer activities. We previously reported that NAG-1 is translocated to different subcellular compartments and its activity depends on its localization. In this paper, we report that the transfection of a novel peptide corresponding to the nuclear localization signal (NLS) of NAG-1 blocks its translocation to the nucleus. Further, accumulation of NAG-1 in the cytoplasm decreased mitochondrial membrane potential, thus implying apoptosis induction as a consequence. Overall, our results indicate that the novel peptide derived from NAG-1 NLS sequence is a promising tool for enhancing the anti-tumorigenic activity of NAG-1.

Keywords: GDF15; High-content screening; Mitochondrial membrane potential; NAG-1; Nuclear localization signal; Peptide transfection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Growth Differentiation Factor 15 / genetics
  • Growth Differentiation Factor 15 / metabolism*
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • GDF15 protein, human
  • Growth Differentiation Factor 15