Bcl-2 protects lymphoma cells from apoptosis but not growth arrest promoted by cAMP and dexamethasone

Glucocorticoids or increases in cellular cAMP promote apoptosis in many cel l types, including murine S49 cells. We examined the impact of Bcl-2, an an tiapoptotic protein, on S49 cell growth and death promoted by the glucocort icoid dexamethasone or agents that increase cAMP: isoproterenol (a beta -ad renergic agonist) + 3-isobutyl-1methylxanthine (a phosphodiesterase inhibit or) and forskolin (diterpene). These agents promoted apoptosis (i.e., incre ased expression of annexin V) of wild-type (WT) S49 cells, but Bcl-2-overex pressing S49 cells were protected from this response. Bcl-2 overexpression did not protect cells from G(1) growth arrest but did allow cells to grow l onger in culture and protected cells from culture-dependent necrosis. Commi tment to and reversal from apoptosis vs. G(1) growth arrest by isoprotereno l + 3-isobutyl-1-methylxanthine showed different kinetics. Although both pr ocesses required several hours to develop, removal of agonists readily reve rsed growth arrest, but not apoptosis. Thus commitment to apoptosis is less reversible than G(1) growth arrest. The findings also indicate that glucoc orticoid- and cAMP-mediated G(1) growth arrest is unaffected by Bcl-2 overe xpression, even though increased Bcl-2 allows these lymphoma cells to resis t necrosis and apoptosis.