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

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...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2019-10, Vol.519 (1), p.29-34
Main Authors: Lee, Jaehak, Kim, Ilju, Yoo, Eunsu, Baek, Seung Joon
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Cell Proliferation - drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
GDF15
Growth Differentiation Factor 15 - genetics
Growth Differentiation Factor 15 - metabolism
HCT116 Cells
HEK293 Cells
High-content screening
Humans
Mitochondrial membrane potential
NAG-1
Nuclear localization signal
Peptide transfection
Structure-Activity Relationship
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Summary: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. [Display omitted] •Accumulation of NAG-1 in the cells results in the induction of cell death.•Nuclear localization Signal peptide from NAG-1 can be transfected into cells and inhibits NAG-1 translocation.•This NLS peptide could be a good tool to induce apoptosis in NAG-1 expressing cells.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2019.08.090