Faculty Collaboration Database

Lithium ions: a novel treatment for pheochromocytomas and paragangliomas. Surgery 2007 Feb;141(2):161-5; discussion 165

Date

02/01/2007

Pubmed ID

17263970

Pubmed Central ID

PMC1945109

DOI

10.1016/j.surg.2006.12.005

Scopus ID

2-s2.0-33846470036 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

BACKGROUND: Operative resection is the only curative treatment for patients with pheochromocytomas, paragangliomas, and other catecholamine-producing neoplasms. Activation of glycogen synthase kinase 3beta (GSK3beta) is thought to promote tumor growth and neuroendocrine (NE) peptide secretion in NE neoplasms. Thus, we hypothesized that inhibition of this signaling pathway with lithium chloride (LiCl), a well-known GSK3beta inhibitor, could be a potential therapeutic strategy to control tumor growth and hormone production.

METHODS: Pheochromocytoma PC-12 cells were treated with varying concentrations of LiCl (0 to 30 mM). Levels of active and inactive GSK3beta and NE peptides chromogranin A (CgA) and Mash1 were determined by Western blot. Cellular growth was measured by MTT cell-proliferation assay.

RESULTS: At baseline, PC-12 cells had increased active GSK3beta signaling. Treatment of PC-12 cells with increasing dosages of LiCl resulted in dose-dependent inhibition of GSK3beta. Importantly, LiCl inhibited pheochromocytoma cellular proliferation significantly. Furthermore, inhibition of GSK3beta by LiCl was associated with marked suppression of CgA and Mash1 levels.

CONCLUSIONS: These data suggest that GSK3beta inhibition may be a novel strategy to treat pheochromocytoma and other catecholamine-producing neoplasms.

Author List

Kappes A, Vaccaro A, Kunnimalaiyaan M, Chen H

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

Adrenal Gland Neoplasms
Animals
Basic Helix-Loop-Helix Transcription Factors
Cell Proliferation
Chromogranin A
Glycogen Synthase Kinase 3
Glycogen Synthase Kinase 3 beta
Lithium Chloride
PC12 Cells
Paraganglioma
Rats