title: MCF-7 cell apoptosis and cell cycle arrest: non-genomic effects of progesterone and mifepristone (RU-486).
abstract: The pharmacology of progestins includes actions initiated by various cellular targets, including classic receptors characterized as nuclear transcription factors (nPR), G-protein-coupled membrane receptors (mPR), enzymes, membrane channels and transporters. The effects initiated by targets other than nPR are termed non-genomic and there is an increasing recognition that these effects also play an important role in the regulation of cell growth.
  
  
  METHODS
  The nPR-positive breast cancer (MCF-7) and the nPR-negative uterine cervix cancer (C4-I) cell lines were exposed to progesterone (PG) and mifepristone (MF) during a culture period of 96 h. Daily cell count, cell cycle analysis and apoptosis assay were performed.
  
  
  RESULTS
  It was possible to separate the nPR initiated effects (growth stimulation) from the non-genomic effects (growth inhibition) in the MCF-7 cells. Below 1 μM PG treatment gave a small, but distinct increase in cell density which was effectively blocked by MF. Such an effect was absent from the nPR-negative C4-I cells. For a range of concentrations between 1 μM and 100 μM, the effect of both PG and MF developed over time and showed concentration dependency. The PG concentrations needed to reduce cell density by 50% (IC(50)) were 12.8 ± 1.1 μM and 6.5 ± 0.2 μM for the MCF-7 and C4-I cells, respectively. MF appeared to be equally or slightly more potent, with respective IC(50) values of 6.9 ± 0.5 μM and 5.3 ± 0.3 μM. The cell density reduction was both a result of cell cycle arrest and apoptosis. The combination of PG and MF had a potentiated effect on cell density reduction, cell cycle arrest and apoptosis.
  
  
  CONCLUSIONS
  The antiproliferative/cytotoxic effect of PG and MF in concentrations between 1 and 100 μM is of a non-genomic nature.
authors.affiliation: Medical Pharmacology and Toxicology Research Unit, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, N-9037 Tromsø, Norway.
authors.forename: Renathe
authors.initials: R
authors.lastname: Fjelldal
authors.forename: Bjørn T
authors.initials: BT
authors.lastname: Moe
authors.forename: Anne
authors.initials: A
authors.lastname: Ørbo
authors.forename: Georg
authors.initials: G
authors.lastname: Sager
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone