Lithium ions: A novel treatment for pheochromocytomas and paragangliomas

Background. Operative resection is the only curative treatment for patients with pheochromocytomas, paragangliomas, and other catecholamine-producing neoplasms. Activation of glycogen synthase kinase 30 (GSK3 beta) 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 beta 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 beta and NE peptides chromogranin A (CgA) and Mash 1 were determined by Western blot. Cellular growth was measured by MTT cell-proliferation assay. Results. At baseline, PC-12 cells had increased active GSK3 beta signaling. Treatment of PC-12 cells with increasing dosage's of LiCl resulted in dose-dependent inhibition of GSK3 beta. Importantly, LiCl inhibited pheochromocytoma cellular proliferation significantly. Furthermore, inhibition of GSK3 beta by LiCl was associated with marked suppression of CgA and Mash1 levels. Conclusions. These data suggest that GSK3 beta inhibition may be a novel strategy to treat pheochromocytoma and other catecholamine prod? icing neoplasms.