Description
Bortezomib is a proteasome inhibitor that displays anticancer chemotherapeutic and antiviral activity in vitro, in vivo, and in clinical settings; it is clinically used or in trials for treatment of glioma, acute lymphoblastic leukemia (ALL), mantle cell lymphoma, and multiple myeloma. In glioma cells, bortezomib induces activation of caspase 3 and apoptosis; its inhibition of the proteasome stimulates angiogenesis through an increase in production of VEGF and HIF-1α. In colorectal cancer cells, bortezomib increased levels of ROS, inducing G2/M phase cell cycle arrest. Additionally, bortezomib induces neuropathy, potentially through increasing polymerized tubulin levels in neurons. In models of Rift Valley Fever Virus, bortezomib decreases viral load by suppressing nonstructural S-segment protein formation of nuclear filaments.
References
Keck F, Amaya M, Kehn-Hall K, et al. Characterizing the effect of Bortezomib on Rift Valley Fever Virus multiplication. Antiviral Res. 2015 May 19. [Epub ahead of print]. PMID: 26001632.
Bota DA, Alexandru D, Keir ST, et al. Proteasome inhibition with bortezomib induces cell death in GBM stem-like cells and temozolomide-resistant glioma cell lines, but stimulates GBM stem-like cells' VEGF production and angiogenesis. J Neurosurg. 2013 Dec;119(6):1415-23. PMID: 24093630.
Staff NP, Podratz JL, Grassner L, et al. Bortezomib alters microtubule polymerization and axonal transport in rat dorsal root ganglion neurons. Neurotoxicology. 2013 Dec;39:124-31. PMID: 24035926.
Du XL, Chen Q. Recent advancements of bortezomib in acute lymphocytic leukemia treatment. Acta Haematol. 2013;129(4):207-14. PMID: 23295437.
Hong YS, Hong SW, Kim SM, et al. Bortezomib induces G2-M arrest in human colon cancer cells through ROS-inducible phosphorylation of ATM-CHK1. Int J Oncol. 2012 Jul;41(1):76-82. PMID: 22552540.
