Faculty Collaboration Database

MG-132 inhibits carcinoid growth and alters the neuroendocrine phenotype. J Surg Res 2010 Jan;158(1):15-9

Date

09/22/2009

Pubmed ID

19765735

Pubmed Central ID

PMC2795050

DOI

10.1016/j.jss.2009.05.032

Scopus ID

2-s2.0-71649102450 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

BACKGROUND: Carcinoid cancers are the most common neuroendocrine (NE) tumors, and limited treatment options exist. The inhibition of glycogen synthase kinase-3beta (GSK-3beta) has been shown to be a potential therapeutic target for the treatment of carcinoid disease. In this study, we investigate the ability of MG-132, a proteasome inhibitor, to inhibit carcinoid growth, the neuroendocrine phenotype, and its association with GSK-3beta.

MATERIALS AND METHODS: Human pulmonary (NCI-H727) and gastrointestinal (BON) carcinoid cells were treated with MG-132 (0-4microM). Cellular growth was measured by the 3-[4,5-dimethylthiazole-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Levels of total and phosphorylated GSK-3beta and the NE markers chromogranin A (CgA), Achaete-Scute complex-like 1 (ASCL1), as well as the apoptotic markers poly (ADP-ribose), polymerase (PARP), and cleaved caspase-3 were determined by Western blot.

RESULTS: Treating carcinoid cells with MG-132 resulted in growth inhibition, a dose-dependent inhibition of CgA and ASCL1, as well as an increase in the levels of cleaved PARP and cleaved caspase-3. Additionally, an increase in the level of phosphorylated GSK-3beta was observed.

CONCLUSION: MG-132 inhibits cellular growth and the neuroendocrine phenotype. This proteasome inhibitor warrants further preclinical investigation as a possible therapeutic strategy for intractable carcinoid disease.

Author List

Chen JY, Cook MR, Pinchot SN, Kunnimalaiyaan M, Chen H

MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents
Apoptosis
Basic Helix-Loop-Helix Transcription Factors
Carcinoid Tumor
Cell Proliferation
Chromogranin A
Cysteine Proteinase Inhibitors
Glycogen Synthase Kinase 3
Glycogen Synthase Kinase 3 beta
Humans
Leupeptins
Neurosecretory Systems
Phenotype
Phosphorylation
Tumor Cells, Cultured