Effects of progesterone and anti-progestin (mifepristone) treatment on proliferation and apoptosis of the human ovarian cancer cell line, OVCAR-3.
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.
Fauvet
Raffaèle
R
Service de Gynécologie-Obstétrique, Hôpital Tenon, Faculté Saint-Antoine, Assistance Publique des Hôpitaux de Paris, Paris, France.
Dufournet Etienne
Charlotte
C
Poncelet
Christophe
C
Bringuier
Annie-France
AF
Feldmann
Gérard
G
Daraï
Emile
E
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005840:Gentian Violet; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007211:Indoles; D008856:Microscopy, Fluorescence; D015735:Mifepristone / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D006727:Hormone Antagonists; D007211:Indoles; D019253:Proto-Oncogene Proteins c-bcl-2; D015735:Mifepristone; C007293:DAPI; D011374:Progesterone; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005840:Gentian Violet