Document Detail


Effects of progesterone and anti-progestin (mifepristone) treatment on proliferation and apoptosis of the human ovarian cancer cell line, OVCAR-3.
MedLine Citation:
PMID:  16525653     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The study examined the effects of various progesterone and mifepristone concentrations on the proliferation and apoptosis of the human ovarian cancer cell line, OVCAR-3. OVCAR-3 cells were incubated with progesterone and mifepristone at concentrations ranging from 10(-3) to 10(-9) M. Proliferation and apoptosis were studied by means of inverted optical microscopy, DAPI staining, and crystal violet assay. Immunoblotting was used to study the regulation of the apoptosis-related proteins, bcl-2, caspase-3 and PARP, after incubation with various reagents. OVCAR-3 cell density was increased by progesterone concentrations of 10(-5) M or less, and decreased by 10(-3) M progesterone. DAPI staining showed no apoptotic bodies. Mifepristone concentrations of 10(-3) and 10(-4) M reduced the OVCAR-3 cell density. Immunoblotting showed PARP cleavage in the presence of mifepristone 10(-4) M. Caspase-3 and bcl-2 expression was reduced by mifepristone 10(-4) and 10(-7) M. These results suggest that progesterone has a paradoxical effect on OVCAR-3 cell proliferation, stimulating it at low concentrations and inhibiting it at high concentrations, potentially through a caspase-independent non-apoptotic death pathway. Mifepristone seems to inhibit OVCAR-3 cell proliferation by down-regulating bcl-2 and up-regulating caspase-3 activity. These preliminary results suggest that progesterone and mifepristone have beneficial effects in ovarian cancer.
Authors:
Raffaèle Fauvet; Charlotte Dufournet Etienne; Christophe Poncelet; Annie-France Bringuier; Gérard Feldmann; Emile Daraï
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oncology reports     Volume:  15     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-09     Completed Date:  2006-07-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  743-8     Citation Subset:  IM    
Affiliation:
Service de Gynécologie-Obstétrique, Hôpital Tenon, Faculté Saint-Antoine, Assistance Publique des Hôpitaux de Paris, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Caspase 3
Caspases / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects*
Dose-Response Relationship, Drug
Female
Gentian Violet
Hormone Antagonists / pharmacology
Humans
Immunoblotting
Indoles
Microscopy, Fluorescence
Mifepristone / pharmacology*
Ovarian Neoplasms / metabolism,  pathology
Poly(ADP-ribose) Polymerases / metabolism
Progesterone / pharmacology*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Chemical
Reg. No./Substance:
0/Hormone Antagonists; 0/Indoles; 0/Proto-Oncogene Proteins c-bcl-2; 47165-04-8/DAPI; 548-62-9/Gentian Violet; 57-83-0/Progesterone; 84371-65-3/Mifepristone; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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