Bortezomib congeners induce apoptosis of hepatocellular carcinoma via CIP2A inhibition
Journal
Molecules
Journal Volume
18
Journal Issue
12
Pages
15398-15411
Date Issued
2013
Author(s)
Kuen-Feng Chen
Abstract
CIP2A is an oncoprotein that upregulates p-Akt and promotes cancer cell proliferation and survival. The proteasome inhibitor bortezomib has been shown to reduce CIP2A and lead to cell apoptosis. Here; we modified the functional group of bortezomib to generate a series of novel compounds and conducted a structure-activity relationship (SAR) study. The results showed that compound 1 was able to repress CIP2A expression and cell apoptosis in the same manner as bortezomib, but with less potency in inhibition of proteasome activity. This finding provides a new direction for the design of CIP2A inhibitors. ? 2013 by the authors; licensee MDPI, Basel, Switzerland.
Subjects
Apoptosis; Bortezomib; CIP2A
SDGs
Other Subjects
antineoplastic agent; autoantigen; boronic acid derivative; bortezomib; KIAA1524 protein, human; membrane protein; pyrazine derivative; apoptosis; article; cell proliferation; cell survival; chemical structure; chemistry; drug antagonism; drug effect; gene silencing; genetics; human; IC 50; liver cell carcinoma; liver tumor; metabolism; structure activity relation; synthesis; tumor cell line; Antineoplastic Agents; Apoptosis; Autoantigens; Boronic Acids; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Cell Survival; Gene Knockdown Techniques; Humans; Inhibitory Concentration 50; Liver Neoplasms; Membrane Proteins; Molecular Structure; Pyrazines; Structure-Activity Relationship
Type
journal article