title: 7 Methyl indole ethyl isothiocyanate causes ROS mediated apoptosis and cell cycle arrest in endometrial cancer cells.
abstract: OBJECTIVE
  Chemotherapy options for advanced endometrial cancer are limited and newer therapeutic agents are urgently needed. This study describes the therapeutic potential of 7 Methyl-indole ethyl isothiocyanate (7Me-IEITC) in endometrial cancer cell lines.
  
  
  METHODS
  7Me-IEITC was synthesized in our laboratory. The cell viability of 7Me-IEITC treated ECC-1 and KLE endometrial cancer cell was determined by MTS assay. Morphology and apoptosis were further confirmed by DAPI-staining and TUNEL assay. The measurement of reactive oxygen species (ROS), mitochondrial transmembrane depolarization potential (ΔΨm) and cell cycle phase was determined by FACS analysis. Expression of proteins involved in apoptosis, survival and cell-cycle progression was analyzed by Western blotting.
  
  
  RESULTS
  7Me-IEITC reduced the viability of the ECC-1 and KLE cancer cell-lines (IC(50)~2.5-10 μM) in a dose dependent fashion. 7Me-IEITC treatment caused mitochondrial transmembrane potential reduction, elevated the production of ROS, leading to activation of apoptosis in endometrial cancer KLE and ECC-1 cells. 7Me-IEITC treatment activated Bad, suppressed Bcl2 phosphorylation followed by PARP-1 deactivation and caspase 3 and 7 activation. 7Me-IEITC treatment arrested the progression of KLE cells in S-phase and caused CDC25 and cyclin-D1 downregulation. Pre-treatment with ascorbic acid abrogated 7Me-IEITC induced apoptosis in ECC-1 and KLE cells, suggesting that 7Me-IEITC mediated cytotoxicity is primarily through ROS production.
  
  
  CONCLUSIONS
  7Me-IEITC demonstrated promising cytotoxic effects in endometrial cancer cell line model.
authors.affiliation: Molecular Therapeutics Laboratory, Program in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants Hospital of Rhode Island, Alpert Medical School, Brown University, Providence, RI 02905, USA.
authors.forename: Katrin
authors.initials: K
authors.lastname: Kristjansdottir
authors.forename: Kyukwang
authors.initials: K
authors.lastname: Kim
authors.forename: Joong Sub
authors.initials: JS
authors.lastname: Choi
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Horan
authors.forename: Laurent
authors.initials: L
authors.lastname: Brard
authors.forename: Richard G
authors.initials: RG
authors.lastname: Moore
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Singh
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D017953:Isocyanates / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: C529237:7-methyl-indole ethyl isothiocyanate; D007211:Indoles; D017953:Isocyanates; D017382:Reactive Oxygen Species