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.

MATERIALS AND 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.

CONCLUSION

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.