Inhibition of rat pituitary tumor cell proliferation by benzodiazepines in vitro

The effect of various benzodiazepines (peripheral-type receptor ligands: Ro 5-4864, PK 11135; central-type receptor ligands: clonazepam, Ro 15-1788, Ro 15-4513; mixed type: diazepam) on the proliferation of estrogen-induced rat pituitary prolactin-secreting tumor cells was studied in vitro. [3H]thymidine incorporation into DNA was used as an index of cell proliferation. It was found that tested peripheral- and mixed-type benzodiazepine receptor ligands significantly suppressed the pituitary cell proliferation in a dose-dependent manner (10(-4)-10(-8) M). The inhibitory effect of Ro 5-4864 was reversed by 5 x 10(-3) M calcium chloride. On the other hand, central-type benzodiazepine receptor ligands suppressed tumor cell proliferation only at the highest concentration studied (10(-4) M). Our results indicate that benzodiazepines might exert an antiproliferative action on pituitary tumor cell growth, and that this effect seems to be a calcium-dependent process.