Journal
CELLS
Volume 9, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/cells9051110
Keywords
GSK-3; targeted therapy; natural products; drug resistance
Categories
Funding
- East Carolina University Grants [111104, 111110-668715-0000]
- Fondazione del Monte di Bologna e Ravenna Research grant
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Glycogen synthase kinase 3 (GSK-3) is a serine/threonine (S/T) protein kinase. Although GSK-3 originally was identified to have functions in regulation of glycogen synthase, it was subsequently determined to have roles in multiple normal biochemical processes as well as various disease conditions. GSK-3 is sometimes referred to as a moonlighting protein due to the multiple substrates and processes which it controls. Frequently, when GSK-3 phosphorylates proteins, they are targeted for degradation. GSK-3 is often considered a component of the PI3K/PTEN/AKT/GSK-3/mTORC1 pathway as GSK-3 is frequently phosphorylated by AKT which regulates its inactivation. AKT is often active in human cancer and hence, GSK-3 is often inactivated. Moreover, GSK-3 also interacts with WNT/beta -catenin signaling and beta -catenin and other proteins in this pathway are targets of GSK-3. GSK-3 can modify NF-kappa B activity which is often expressed at high levels in cancer cells. Multiple pharmaceutical companies developed small molecule inhibitors to suppress GSK-3 activity. In addition, various natural products will modify GSK-3 activity. This review will focus on the effects of small molecule inhibitors and natural products on GSK-3 activity and provide examples where these compounds were effective in suppressing cancer growth.
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