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Targeting GSK3 and Associated Signaling Pathways Involved in Cancer

Przemysław Duda1, Shaw M Akula2, Stephen L Abrams2

  • 1Department of Molecular Physiology and Neurobiology, University of Wrocław, Sienkiewicza 21, 50-335, Wroclaw, Poland.

Cells
|May 6, 2020
PubMed

Insights

Glycogen synthase kinase 3 (GSK-3) is a key protein kinase involved in numerous cellular processes and diseases. This review explores how small molecule inhibitors and natural products targeting GSK-3 can suppress cancer growth.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase with diverse roles in cellular functions.
  • GSK-3 is implicated in various disease conditions, including cancer, often due to its inactivation in pathways like PI3K/AKT.
  • It acts as a moonlighting protein, phosphorylating multiple substrates, frequently targeting them for degradation and influencing signaling pathways such as WNT/β-catenin and NF-κB.

Purpose of the Study:

  • To review the effects of small molecule inhibitors and natural products on GSK-3 activity.
  • To provide examples of compounds that effectively suppress cancer growth by modulating GSK-3.

Main Methods:

  • Literature review of studies investigating GSK-3 inhibitors and natural products.
  • Analysis of signaling pathways involving GSK-3, including PI3K/AKT, WNT/β-catenin, and NF-κB.
  • Compilation of evidence demonstrating the efficacy of GSK-3 modulators in preclinical cancer models.

Main Results:

  • Small molecule inhibitors have been developed to suppress GSK-3 activity.
  • Natural products also exhibit the ability to modify GSK-3 activity.
  • Several compounds targeting GSK-3 have shown effectiveness in suppressing cancer cell proliferation and tumor growth in experimental settings.

Conclusions:

  • GSK-3 is a significant target for cancer therapy.
  • Inhibitors of GSK-3, including those derived from natural products, hold promise for cancer treatment.
  • Further research into GSK-3 modulators could lead to novel therapeutic strategies for various cancers.
Keywords:
GSK-3drug resistancenatural productstargeted therapy

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