Lithium ions: A novel treatment for pheochromocytomas and paragangliomas

• Published in: Surgery Vol. 141; no. 2; pp. 161 - 165
• Main Authors: Kappes, Ashley, BS, Vaccaro, Abram, BS, Kunnimalaiyaan, Muthusamy, PhD, Chen, Herbert, MD, FACS
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.02.2007
• Subjects: Adrenal Gland Neoplasms - drug therapy; Animals; Basic Helix-Loop-Helix Transcription Factors - drug effects; Cell Proliferation - drug effects; Chromogranin A - drug effects; Glycogen Synthase Kinase 3 - antagonists & inhibitors; Glycogen Synthase Kinase 3 beta; Lithium Chloride - pharmacology; Lithium Chloride - therapeutic use; Paraganglioma - drug therapy; PC12 Cells; Rats; Surgery
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2006.12.005

Background Operative resection is the only curative treatment for patients with pheochromocytomas, paragangliomas, and other catecholamine-producing neoplasms. Activation of glycogen synthase kinase 3 β (GSK3 β ) 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 GSK3 β 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 GSK3 β 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 GSK3 β signaling. Treatment of PC-12 cells with increasing dosages of LiCl resulted in dose-dependent inhibition of GSK3 β . Importantly, LiCl inhibited pheochromocytoma cellular proliferation significantly. Furthermore, inhibition of GSK3 β by LiCl was associated with marked suppression of CgA and Mash1 levels. Conclusions These data suggest that GSK3 β inhibition may be a novel strategy to treat pheochromocytoma and other catecholamine-producing neoplasms.