Lithium induces mortality in medulloblastoma cell lines.
Lithium is the main therapeutic agent for the treatment of bipolar disorders but nerve cells are not the sole target of this drug. Indeed, lithium has been reported to target numerous cell types and to affect cell proliferation, differentiation and death. Lithium targets a variety of enzymes among which there is GSK-3beta and a number of cell responses elicited by lithium are mediated by the Wnt pathway that is involved in medulloblastoma (MB) pathogenesis. We studied the in vitro effects of lithium on two different MB cell lines: D283MED and DAOY. High doses of lithium inhibited GSK3-beta, decreased cell proliferation and induced non-apoptotic cell death in both cell lines independently by intracellular levels of beta-catenin that is consistently high only in D283MED. At clinical doses, the anti-neoplastic effects were observed only in this cell line, highlighting the importance of a specific molecular background in determining the target therapy response. In conclusion, lithium could be a promising drug in MB, but an accurate molecular profile predictive of drug response still needs to be clarified.
Ronchi
Alice
A
Clinical Department of Radiological and Histopathological Sciences, University of Bologna Alma Mater Studiorum, Via Massarenti 9, 40138 Bologna, Italy.
Salaroli
Roberta
R
Rivetti
Stefano
S
Della Bella
Elena
E
Di Tomaso
Tiziano
T
Voltattorni
Manuela
M
Cammelli
Silvia
S
Ceccarelli
Claudio
C
Giangaspero
Felice
F
Barbieri
Enza
E
Cenacchi
Giovanna
G
D016923:Cell Death / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D016158:Genes, p53; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology*; D008527:Medulloblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009154:Mutation; D051153:Wnt Proteins / Q000378:metabolism
D051153:Wnt Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride