title: Induction of mitochondrial apoptotic pathway by raloxifene and estrogen in human endometrial stromal ThESC cell line.
abstract: BACKGROUND
  Endometrial hyperplasia is a condition that occurs as a result of hormonal imbalance between estrogen and progesterone. Morphological disturbance of endometrial cells occurs consequently leading towards endometrial cancer. In therapy of endometrial hyperplasia SERMs are used to supress effects of locally high estrogen level in uterus. There is strong evidence suggesting that estrogen could be involved in cell death - apoptosis. There are no experimental data demstrating the direct apoptotic effect of both raloxifene and estrogen on the ThESC cell line. The aim of our study wa sto investigate both cytotoxic and apototic mechanism of raloxifene and estrogen - induced death in the ThESC cell line.
  
  
  METHODS
  In order to determine their cytotoxic and apoptotic effects, various doses of raloxifene and estrogen were applied to the ThESC cell line for 24 h. After the treatment MTT assay, FACS analysis and immunofluoroscence method were conducted.
  
  
  RESULTS
  The results of this study for the first time demonstrated the cytotoxic and apoptotic effects of raloxifene and estrogen on human endometrial stromal cell line suggesting the involvement of the inner, mitochondrial apoptotic pathway.
  
  
  CONCLUSIONS
  Our results demonstrated apoptotic effects of investigated drugs in the ThESC cell line through increasing the Bax/Bcl-2 ratio and activation of caspase 3.
authors.affiliation: Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Nikolic
authors.affiliation: Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Andjelkovic
authors.affiliation: Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Milan
authors.initials: M
authors.lastname: Zaric
authors.affiliation: Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Ivanka
authors.initials: I
authors.lastname: Zelen
authors.affiliation: Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Petar
authors.initials: P
authors.lastname: Canovic
authors.affiliation: Department of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, Serbia.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Milosavljevic
authors.affiliation: Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Mitrovic
keywords: apoptosis; endometrial hyperplasia; estrogen; inner apoptotic pathway; raloxifene