title: Lipoic acid decreases Mcl-1, Bcl-xL and up regulates Bim on ovarian carcinoma cells leading to cell death.
abstract: BACKGROUND
  Ovarian carcinoma is the leading cause of death from gynecological cancer because there is risk of chemoresistance. As previously demonstrated in our laboratory, Alpha-lipoic acid (LA), a co-factor for metabolic enzymes, suppresses the tumor growth. In this study, we have researched the mechanisms that are responsible for the activity of LA.
  
  
  METHODS
  We have studied the mechanisms of LA in two ovarian cancer cell lines, a cisplatin sensitive one, IGROV1 and its resistant counterpart, IGROV1-R10. These cells have been exposed to lipoic acid at various concentrations. Cell proliferation, cell cycle repartition and nuclear staining with DAPI were recorded. Western blot analyses were performed to detect various proteins implied in apoptotic cell death pathways. To investigate the formation of ROS, the oxidation of CM-DCFH2-DA were also determined.
  
  
  RESULTS
  LA suppressed growth proliferation and induced apoptosis in both ovarian cell lines. Moreover, LA provoked a down regulation of two anti-apoptotic proteins, Mcl-1 and Bcl-xL protein and a strong induction of the BH3-only protein Bim. Furthermore, LA induced ROS generation which could be involved in the CHOP induction which is known to activate the Bim translation.
  
  
  CONCLUSIONS
  Our results reveal novel actions of LA which could explain the anti-tumoral effects of the LA. Therefore, LA seems to be a promising compound for ovarian cancer treatment.
authors.affiliation: INSERM, U 1199, Unité BioTICLA, Caen, F-14032, France. perrinekafara@hotmail.fr.|Normandie Université France, Caen, France. perrinekafara@hotmail.fr.|Centre de Lutte Contre le Cancer François Baclesse, Avenue du Général Harris, Caen, BP5026 14076, Cedex 05, France. perrinekafara@hotmail.fr.
authors.forename: Perrine
authors.initials: P
authors.lastname: Kafara
authors.affiliation: INSERM, U 1199, Unité BioTICLA, Caen, F-14032, France. philippe.icard@hotmail.fr.|Normandie Université France, Caen, France. philippe.icard@hotmail.fr.|Centre de Lutte Contre le Cancer François Baclesse, Avenue du Général Harris, Caen, BP5026 14076, Cedex 05, France. philippe.icard@hotmail.fr.|UMR 7161, Laboratoire d'Informatique LIX, Ecole Polytechnique, 91128, Palaiseau Cedex, France. philippe.icard@hotmail.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Icard
authors.affiliation: INSERM, U 1199, Unité BioTICLA, Caen, F-14032, France. m.guillamin@baclesse.fr.|Normandie Université France, Caen, France. m.guillamin@baclesse.fr.|Centre de Lutte Contre le Cancer François Baclesse, Avenue du Général Harris, Caen, BP5026 14076, Cedex 05, France. m.guillamin@baclesse.fr.
authors.forename: Marilyne
authors.initials: M
authors.lastname: Guillamin
authors.affiliation: UMR 7161, Laboratoire d'Informatique LIX, Ecole Polytechnique, 91128, Palaiseau Cedex, France. schwartz@lix.polytechnique.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schwartz
authors.affiliation: UMR INSERM U1052, CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France. hubert.lincet@univ-lyon1.fr.|ISPB, Faculté de Pharmacie de Lyon, 8 avenue Rockefeller, F69373, Lyon, Cedex 08, France. hubert.lincet@univ-lyon1.fr.|Université de Lyon 1, Lyon, France. hubert.lincet@univ-lyon1.fr.
authors.forename: Hubert
authors.initials: H
authors.lastname: Lincet
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D000072224:Bcl-2-Like Protein 11; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D008063:Thioctic Acid / Q000008:administration & dosage; D051020:bcl-X Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C579095:MCL1 protein, human; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011518:Proto-Oncogene Proteins; D051020:bcl-X Protein; D008063:Thioctic Acid; D002945:Cisplatin