Genistein induces a G2/M block and apoptosis in human uterine adenocarcinoma cell lines.

We report evidence indicating that the isoflavone genistein induces a dose-dependent antiproliferative effect in the human uterine adenocarcinoma cell lines HEC-1A, HEC-1B, AN3 CA and RL95-2. Cell growth inhibition resulted from a partial G(2)/M block and from the appearance of a hypodiploid DNA peak (reduction in nuclear DNA content), suggestive of apoptosis. In HEC-1A cells, we found that both cell cycle impairment and the appearance of a hypodiploid DNA peak were time-dependent, triggered by similar concentrations of the isoflavone and not affected by the presence of serum in the culture medium. However, while the genistein-induced cell cycle arrest was fully reversible, the appearance of the hypodiploid DNA peak was not. To verify whether the appearance of a hypodiploid DNA peak corresponded to apoptosis, we used in situ end labelling (ISEL) and transmission electron microscopy (TEM) in HEC-1A cells. We found that a 48-h treatment with genistein induced ISEL positivity only in a minority of cells, while at 72 h the majority of cells were labelled. At this time TEM showed the typical ultrastructural features of apoptosis, including apoptotic bodies.