Title:Pharmacological Activation of Protein Phosphatase 2 A (PP2A): A Novel Strategy to Fight Against Human Malignancies?
Volume: 23
Issue: 38
Author(s): Maria Rosaria Carratù, Anna Signorile, Domenico De Rasmo, Antonia Reale and Angelo Vacca
Affiliation:
Keywords:
Protein phosphatase 2 A, cancer, fingolimod, bortezomid, forskolin, carnosic acid.
Abstract: Background: The serine-threonine protein phosphatase 2A (PP2A) regulates
multiple cell signaling cascades and its inactivation by viral oncoproteins, mutation of specific
structural subunits or upregulation of the cellular endogenous inhibitors may contribute
to malignant transformation by regulating specific phosphorylation events. Pharmacological
modulation of PP2A activity is becoming an attractive strategy for cancer treatment. Some
compounds targeting PP2A are able to induce PP2A reactivation and subsequent cell death
in several types of cancer.
Methods: We undertook a search of bibliographic databases for peer-reviewed articles focusing
on the main item of the review. We selected articles published in indexed journals.
The quality of retrieved papers was appraised using the standard bibliometric indicators.
Results: One hundred and fourteen papers were included in the review. Twenty-seven papers
gave an overview of structure and physiological role of PP2A. Twenty-five papers outlined
the role of PP2A in tumor suppression. Forty papers analyzed the mechanism involved
in PP2A reactivation by synthetic compounds, and twenty-two papers outlined the capability
of natural compounds of restoring PP2A activity and how this could be beneficial.
Conclusion: Findings analyzed in this review underline the central role of PP2A as a regulator
of cell growth and survival, hence its function as tumor suppressor. The discovery that
some compounds, either synthetic or natural, are capable of reactivating PP2A opens up
new perspectives for future strategies to fully exploit therapeutic potential in human cancer.
Thus, this review could also be of particular interest to pharmaceutical or biotechnology
companies for drug design and targeted delivery.
