Non-genomic Cell Growth Inhibition by Progesterone. Cell Cycle Retardation and Induction of Cell Death

Abstract

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 μM (mean value±SEM, n=4). At 320 μM 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.