title: Inhibition of endometrial cancer cell lines by mifepristone (RU 486).
abstract: OBJECTIVE
  To determine the role of mifepristone (RU 486) in the growth of endometrial cancer cell lines, and the mechanism associated with this regulation.
  
  
  METHODS
  Three endometrial cancer cell lines (Hec-1A, KLE, and RL95-2) were used in this study. Growth inhibition was demonstrated by sulforhodamine B cytotoxicity assay. Mode of inhibition by RU 486 was studied by induction of DNA fragmentation. The effect of RU 486 on steady-state accumulation of the progesterone and glucocorticoid receptors (PRs and GRs, respectively) and apoptosis-associated gene products was studied by Western blotting.
  
  
  RESULTS
  We demonstrated a dose-dependent inhibition of growth in all of the three endometrial cancer cell lines. Following treatment with 5.0 micrograms/mL of RU 486, there was 39.3%, 66.3%, and 75.5% inhibition of KLE, Hec-1A, and RL95-2 cells, respectively. Decreased expression of GR in RL95-2 (0.1-10 micrograms/mL) and in KLE cells (10 micrograms/mL) was observed. A marked decrease of PR was seen with RL95-2 cells at 10 micrograms/mL, there was no change in the KLE cells, and a dose-dependent decrease was seen with Hec-1A cells. Various levels of apoptosis were demonstrated by DNA fragmentation in all three cell lines. Of the genes associated with apoptosis, dose-dependent reduction of bax expression was demonstrated in KLE cells, while induction of WAF-1 was seen in Hec-1A and RL95-2 cells, and reduction of bcl-2 was demonstrated in RL95-2 cells.
  
  
  CONCLUSIONS
  Clinically achievable doses of RU 486 inhibit endometrial cancer cell lines. The mechanism of inhibition involves apoptosis, and regulation of bax, bcl-2, and WAF-1 is demonstrated. Therapeutic application of these findings remains to be determined.
authors.affiliation: Department of Obstetrics and Gynecology, University of Louisville School of Medicine, Kentucky 40202, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Schneider
authors.forename: R K
authors.initials: RK
authors.lastname: Gibb
authors.forename: D D
authors.initials: DD
authors.lastname: Taylor
authors.forename: T
authors.initials: T
authors.lastname: Wan
authors.forename: C
authors.initials: C
authors.lastname: Gerçel-Taylor
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D015735:Mifepristone / Q000627:therapeutic use*; D011374:Progesterone / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D006727:Hormone Antagonists; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D051028:bcl-2-Associated X Protein; D015735:Mifepristone; D011374:Progesterone