TY - JOUR
T1 - Lithium induces mortality in medulloblastoma cell lines
AU - Ronchi, Alice
AU - Salaroli, Roberta
AU - Rivetti, Stefano
AU - Bella, Elena Della
AU - Di Tomaso, Tiziano
AU - Voltattorni, Manuela
AU - Cammelli, Silvia
AU - Ceccarelli, Claudio
AU - Giangaspero, Felice
AU - Barbieri, Enza
AU - Cenacchi, Giovanna
PY - 2010/9
Y1 - 2010/9
N2 - 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-3β 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-β, decreased cell proliferation and induced non-apoptotic cell death in both cell lines independently by intracellular levels of β-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.
AB - 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-3β 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-β, decreased cell proliferation and induced non-apoptotic cell death in both cell lines independently by intracellular levels of β-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.
KW - Glycogen synthase kinase-3β
KW - Lithium chloride
KW - Medulloblastoma
UR - http://www.scopus.com/inward/record.url?scp=77956504016&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956504016&partnerID=8YFLogxK
U2 - 10.3892/ijo-00000724
DO - 10.3892/ijo-00000724
M3 - Article
C2 - 20664944
AN - SCOPUS:77956504016
VL - 37
SP - 745
EP - 752
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 3
ER -