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).
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: email@example.com