title: LiCl Treatment Induces Programmed Cell Death of Schwannoma Cells through AKT- and MTOR-Mediated Necroptosis.
abstract: Lithium is considered a first-line therapy for the treatment of bipolar disorder and was recently shown to be associated with a reduced overall cancer risk. A growing body of evidence has indicated the potential antitumor benefits of this drug. Lithium likely functions as an antitumor agent. In this study, we found that lithium chloride (LiCl) significantly inhibits the proliferation of both RT4 cells and human NF2-associated primary schwannoma cells by inhibiting the expression of apoptosis-related proteins. LiCl-induced cell death exhibits ultrastructural features of necrosis and is reversed by the RIPK1-specific inhibitor necrostatin-1 in a dose-dependent manner, indicating that LiCl induces the necroptosis type of cell death. Moreover, LiCl treatment induces ROS generation and activates the AKT/mTOR pathway, which is reversed by necrostatin-1 treatment. Based on our results, LiCl treatment may induce the programmed cell death of schwannoma cells through AKT- and mTOR-mediated necroptosis, potentially representing a new mechanism by which LiCl induces tumor cell death. Moreover, LiCl may prove to be a new drug for treating schwannoma.
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. liupinan@yeah.net.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. liupinan@yeah.net.
authors.forename: Pinan
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology* / Q000627:therapeutic use; D009336:Necrosis / Q000378:metabolism; D009442:Neurilemmoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016518:Neurofibromatosis 2 / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D018021:Lithium Chloride
keywords: AKT; LiCl; NF2; Necroptosis; Schwannoma; mTOR