Thomas Mayerhofer and Rajesh Kumar Jha* Pages 78 - 88 ( 11 )
Background: Regulation of protein phosphatase 2A (PP2A) plays an important role in hematologic and solid neoplasms. Therefore, the use of sphingosine analogs as anti-neoplastic drugs has shown potential due to their role as PP2A activators.
Objective: Investigation of whether sphingosine analogs bind to endogenous inhibitor proteins of PP2A, such as I2 PP2A/SET and/or CIP2A, and whether this binding reactivates PP2A, allowing it to resume its role as a tumor suppressor.
Methods: Literature from the PubMed database was searched and those articles related to PP2A and sphingosine analogs were reviewed.
Results: Utilization of sphingosine analogs in hematologic and solid neoplasms revealed numerous mechanisms of inducing cell death. Regulation of PP2A through modulation of I2 PP2A/SET and/or CIP2A was demonstrated in a variety of neoplastic processes; however, unique mechanisms such as cell necrosis via the production of reactive oxygen species was also appreciated.
Conclusion: Only certain malignancies expressed endogenous inhibitor proteins, yet sphingosine analogs were able to induce cell death in neoplasms that did not express these proteins. This suggests that sphingosine analogs may be utilized for anti-neoplastic therapy via reactivation of PP2A however, it is not the exclusive mechanism for inducing cell death. Further investigation of sphingosine analogs as a novel or adjunctive chemotherapeutic treatment is warranted.
PP2A, I2 PP2A/SET, CIP2A, sphingosine analogs, FTY720, S1PR, neoplasm, leukemia.
Department of Pharmacology, Saba University School of Medicine, The Bottom, Saba, Department of Pharmacology, Saba University School of Medicine, The Bottom, Saba