Bromocriptine induced apoptosis in pituitary adenoma cells: relationship to p53 and bcl-2 expression

In an attempt to understand the roles of the tumour suppressor gene p53 and the proto-oncogene bcl-2 in cell death and survival in pituitary adenomas, we investigated the relationship of their expression to the apoptotic resp onse of two pituitary adenoma cell lines (GH3 and AtT-20) to bromocriptine. An MTT (3-4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrasolium bromide) as say was performed after treatment with bromocriptine for various periods of time over a range of concentrations to determine the effect of this drug o n cell growth. Bromocriptine inhibited growth of GH3 and AtT-20 cells in a dose dependent manner. DNA fragmentation was assessed in GH3 and AtT-20 cel ls exposed to 10 ug/ml bromocriptine for 48 h and 72 h. The DNA of GH3 and AtT-20 cells showed nucleosomal fragmentation, indicative of apoptosis. Whe n assayed 2 days after adding bromocriptine, approximately 60% of GH3 and 5 8% of AtT-20 cells treated with bromocriptine displayed typical apoptotic m orphology, including condensed chromatin and fragmented nuclei. There was a time dependent increase in the proportion of all tumour cells undergoing a poptosis. Decreased expression of bcl-2 and accumulation of wild-type p53 w ere associated with bromocriptine induced apoptosis in pituitary adenoma ce lls. DNA analysis confirmed the results obtained by the protein study. Diff erent expression of p53 and bcl-2 genes is Drugs and cells consistent with the expression of these gene products. These findings show that bromocripti ne activated wild-type p53 and suppressed bcl-2 favouring occurrence of apo ptosis in pituitary adenoma cells.