AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 2010;2(3):248-253

Original Article
Lithium inhibits carcinoid cell growth in vitro

David Yu Greenblatt, Mary Ndiaye, Herbert Chen, Muthusamy Kunnimalaiyaan

Endocrine Surgery Research Laboratories, Department of Surgery, University of Wisconsin School of Medicine
and Public Health, and the University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USAd

Received April 14, 2010, accepted April 29, 2010, available online May 10, 2010

Abstract: Carcinoids are slow growing neuroendocrine tumors that often cause debilitating symptoms due to
excessive secretion of hormones such as serotonin. Surgery is the only potentially curative treatment, but many
patients have unresectable metastatic disease. Lithium is a non-competitive inhibitor of GSK-3 with an
established safety profile.  The objective of this study was to investigate the effects of lithium on carcinoid cell
growth in vitro.  Lithium treatment caused a dose-dependent reduction in carcinoid cancer cell (BON and H727)
growth. Western blot analysis revealed increased expression of cleaved poly (ADP-ribose) polymerase (PARP),
indicating the induction of apoptosis. Lithium treatment also suppressed cellular levels of serotonin and
chromogranin A. In summary, lithium inactivates GSK-3, induces apoptosis, and suppresses carcinoid cancer
cell growth  in vitro. The drug has been used clinically since the 19th century to treat a variety of diseases
including bipolar disorder, and its safety profile is well documented. Therefore, based on these findings, we have
undertaken a clinical trial of lithium chloride in the treatment of patients with unresectable carcinoid cancer.
Key Words: Carcinoid Tumors;  BON Cells; Lithium Chloride; Chromogranin A; Achaete-Scute Complex-Like 1;
Serotonin (AJTR1004002).

Key words: Carcinoid tumors, neuroendocrine tumors, H727 cells, BON cells, lithium chloride, chromogranin A,
Achaete-Scute Complex-Like 1, serotonin

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Address all correspondence to:
Muthusamy Kunnimalaiyaan, PhD
Department of SUrgery
University of Wisconsin School of Medicine and Public Health
3028 WIMR, 1111 Highland Avenue
Madison, WI, 53705;
Tel: (608) 263-1387;  Fax: (608) 263-7652
E-mail:
kunni@surgery.wisc.edu