Non-genomic cell growth inhibition by progesterone. cell cycle retardation and induction of cell death.
BACKGROUND
Non-genomic mechanisms have been proposed to play a role in progesterone-dependent cell growth inhibition.


METHODS
The human cell line C-4I, derived from a squamous carcinoma of the uterine cervix, was progesterone receptor-negative. The culture medium contained 10% (v/v) fetal calf serum and the cells, growing in monolayer, were exposed to various progesterone concentrations. Flow cytometry and morphometry were employed to assess the effects.


RESULTS
Progesterone caused a concentration-dependent growth inhibition with an IC50 value of 2.06 +/- 0.46 microM (mean value +/- SEM, n = 4). At 320 microM no viable and attached cells were left. Two mechanisms appeared to be responsible for the effect. Firstly, the cells accumulated in the G1/G0-phase indicating a cell cycle-specific arrest. Secondly, progesterone induced cell death with apoptosis and necrosis. Morphometric analysis showed that progesterone caused a marked reduction in the nuclear size, compatible with apoptosis.


CONCLUSIONS
The present results show that progesterone exerts non-genomic effect(s) by reducing the input of and accelerating the exit of cells from the C-4I cell population.
Bertelsen
Eirin Listau
EL
Department of Pharmacology Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Tromsø, Norway.
Endresen
Petter Cappelen
PC
Orbo
Anne
A
Sager
Georg
G
D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D011374:Progesterone / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
D006131:Growth Inhibitors; D011980:Receptors, Progesterone; D011374:Progesterone