Lithium induces mortality in medulloblastoma cell lines

Alice Ronchi, Roberta Salaroli, Stefano Rivetti, Elena Della Bella, Tiziano Di Tomaso, Manuela Voltattorni, Silvia Cammelli, Claudio Ceccarelli, Felice Giangaspero, Enza Barbieri, Giovanna Cenacchi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)745-752
Number of pages8
JournalInternational Journal of Oncology
Volume37
Issue number3
DOIs
Publication statusPublished - Sep 2010

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Keywords

  • Glycogen synthase kinase-3β
  • Lithium chloride
  • Medulloblastoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ronchi, A., Salaroli, R., Rivetti, S., Bella, E. D., Di Tomaso, T., Voltattorni, M., Cammelli, S., Ceccarelli, C., Giangaspero, F., Barbieri, E., & Cenacchi, G. (2010). Lithium induces mortality in medulloblastoma cell lines. International Journal of Oncology, 37(3), 745-752. https://doi.org/10.3892/ijo-00000724