Effect of bromocriptine on cell apoptosis and proliferation in GH3 cell culture

OBJECTIVES: In our study, with the use of GH(3) cells line we decided to examine 1) what is the relation between the dose of bromocriptine and the development of apoptosis in GH3 cells 2) whether the induction of apoptosis is accompanied by alterations in bcl-2 and p53 content and 3) whether dibutyryl-cAMP or phorbol esters affect the initiation of apoptosis in GH3 cells. RESULTS: The current study demonstrated the absence of alterations in GH3 cells incubated for 24 h with bromocriptine at the concentrations of up to 15 mumol/l. Apoptotic and necrotic changes were observed after 48 h incubation with bromocriptine at the concentrations of 25 mumol/l. The ratio of necrotic to apoptotic cells increased at 40 mumol/l of bromocriptine concentration. An inhibitory effect of bromocriptine on cell proliferation was also observed. Phorbol-12-myristate-13-acetate (PMA), at concentrations ranging between 25 ng to 200 ng/ml, reduced the amount of apoptotic cells. CONCLUSIONS: Application of dibutyryl-cAMP at the concentration of I to 8 mmol/l resulted in an inhibition of apoptosis, followed by an increase in the number of cultured cells. Ultrastructural studies showed evident apoptotic lesions in the cells.