MG-132 Inhibits Carcinoid Growth and Alters the Neuroendocrine Phenotype

Jui yu Chen, Mackenzie R. Cook, Scott N. Pinchot, Muthusamy Kunnimalaiyaan, Herbert Chen

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background: Carcinoid cancers are the most common neuroendocrine (NE) tumors, and limited treatment options exist. The inhibition of glycogen synthase kinase-3β (GSK-3β) 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-3β. Materials and Methods: Human pulmonary (NCI-H727) and gastrointestinal (BON) carcinoid cells were treated with MG-132 (0-4μM). 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-3β 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-3β 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.

Original languageEnglish (US)
Pages (from-to)15-19
Number of pages5
JournalJournal of Surgical Research
Volume158
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Keywords

  • ASCL1
  • MG-132
  • apoptosis
  • carcinoid
  • glycogen synthase kinase-3β
  • proteasome inhibitor

ASJC Scopus subject areas

  • Surgery

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