title: Effect of lithium chloride and antineoplastic drugs on survival and cell cycle of androgen-dependent prostate cancer LNCap cells.
abstract: OBJECTIVE
  Glycogen synthase kinase-3β (GSK-3β) has been reported to be required for androgen receptor (AR) activity. This study sought to determine the usefulness of lithium chloride (LiCl) as a highly selective inhibitor of GSK-3β to increase the sensitivity of LNCap cells to doxorubicin (Dox), etoposide (Eto), and vinblastine (Vin) drugs.
  
  
  METHODS
  Thiazolyl Blue Tetrazolium Blue (MTT) assay was used to determine the cytotoxic effect to LiCl alone or in combination with low dose and IC50 doses of drugs. Subsequently, cell cycle analysis was performed by using flow cytometry.
  
  
  RESULTS
  LiCl showed cytotoxic effect in a dose- and time-dependent manner (P<0.001). Both Dox (100 or 280 nM) and Vin IC50 (5 nM) doses caused G2/M-phase arrest (P<0.001) compared with control. However, low dose (10 μM) or IC50 (70 μM) Eto doses showed G2/M or S-phase arrests, respectively (P<0.001). Combination of low dose or IC50 dose of Eto with LiCl showed increased apoptosis as revealed by high percent of cells in SubG1 (P<0.05, P<0.01, respectively). Moreover, Eto (10 μM) led to decreased percent of cells in G2/M phase when combined with LiCl (P<0.05).
  
  
  CONCLUSIONS
  This study showed that LiCl increases apoptosis of (LNCap) Lymph Node Carcinoma of the Prostate cells in the presence of Eto, which is S- and G2-phase-specific drug.
authors.affiliation: Department of Animal Biology, Developmental Biology Lab., School of Biology, University College of Science, University of Tehran, Tehran, Iran.
authors.forename: Vajihe
authors.initials: V
authors.lastname: Azimian-Zavareh
authors.forename: Ghamartaj
authors.initials: G
authors.lastname: Hossein
authors.forename: Ehsan
authors.initials: E
authors.lastname: Janzamin
mesh_terms: D000728:Androgens; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000008:administration & dosage*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018021:Lithium Chloride / Q000008:administration & dosage*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy; D014747:Vinblastine / Q000008:administration & dosage*
chemical_list: D000728:Androgens; D000970:Antineoplastic Agents; D014747:Vinblastine; D005047:Etoposide; D004317:Doxorubicin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride