title: In vitro mechanisms involved in the regulation of cell survival by lithium chloride and IGF-1 in human hormone-dependent breast cancer cells (MCF-7).
abstract: Lithium, the lightest of all solid elements, has been used for the treatment of bipolar disorder since 1970s and prescribed to millions of women worldwide. Lithium chloride (LiCl) has been considered to be a potent inhibitor of glycogen synthase kinase-3β (GSK-3β), a serine/threonine kinase that is involved in the control of cell proliferation, differentiation, and apoptosis. In addition, GSK-3β has been found to be inhibited endogenously by insulin-like growth factor-1 (IGF-1), a potent mitogen that plays an important role in the survival, growth, and differentiation of normal and neoplastic cells. Although both IGF-1 and LiCl have the ability to inhibit GSK-3β, the specific signaling difference that mediates the survival of breast cancer cells was not clear. Therefore, in the present study, MCF-7 cells (human breast cancer cells) were treated with or without IGF-1 or LiCl in the presence or absence of LY294002 or PD98059 (pharmacological inhibitors) for 24h. As the expression of signaling proteins is crucial in the maintenance of cell survival and apoptosis, we analyzed the cells using immunoblotting procedure. In summary, our results have shown that LiCl and IGF-1 mediates cell survival by inhibiting GSK-3β but differ in their mechanisms. IGF-1 involves PI3K/Akt or MAPK pathways whereas LiCl is completely independent of these pathways. IGF-1 upregulates anti-apoptotic proteins whereas LiCl downregulates apoptotic proteins in order to maintain cell survival.
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
authors.forename: Muralidharan
authors.initials: M
authors.lastname: Suganthi
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Sangeetha
authors.forename: Chellakan Selvanesan
authors.initials: CS
authors.lastname: Benson
authors.forename: Somasundaram Dinesh
authors.initials: SD
authors.lastname: Babu
authors.forename: Anandhan
authors.initials: A
authors.lastname: Sathyavathy
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Ramadoss
authors.forename: Bhaskaran
authors.initials: B
authors.lastname: Ravi Sankar
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D015151:Immunoblotting; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D018021:Lithium Chloride / Q000494:pharmacology*; D061986:MCF-7 Cells; D009025:Morpholines / Q000494:pharmacology; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009930:Organic Chemicals / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D009930:Organic Chemicals; C466090:PD 98058; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007334:Insulin-Like Growth Factor I; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride