RT Journal Article
SR Electronic
T1 Role of Caspase 3-Dependent Bcl-2 Cleavage in Potentiation of Apoptosis by Bcl-2
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 142
OP 149
DO 10.1124/mol.61.1.142
VO 61
IS 1
A1 Liang, Ye
A1 Nylander, Karen D.
A1 Yan, Chaohua
A1 Schor, Nina Felice
YR 2002
UL http://molpharm.aspetjournals.org/content/61/1/142.abstract
AB Previous studies from our laboratory have demonstrated that Bcl-2 has a proapoptotic effect on neocarzinostatin (NCS)-treated PC12 pheochromocytoma cells. In the present study, we examine the mechanisms of this effect and demonstrate its relevance for the in vivo situation. Four hours after NCS treatment, a 23-kDa cleavage product of Bcl-2 was detected in whole cell lysates of bcl-2–transfected PC12 cells. In contrast, bcl-2 transfection protected PC12 cells from cisplatin-induced apoptosis, and cisplatin treatment did not result in Bcl-2 cleavage. Similarly, Bcl-2 cleavage did not occur and Bcl-2-mediated protection from, rather than potentiation of apoptosis was observed after NCS treatment of MCF-7 breast cancer cells. The caspase 3-specific inhibitor Ac-DEVD-CHO prevented Bcl-2 cleavage and attenuated NCS-induced apoptosis inbcl-2–transfected PC12 cells, whereas it had no effect on NCS-induced apoptosis in mock-transfected PC12 cells. Furthermore, MCF-7 cells do not express caspase 3, a finding in concert with the lack of Bcl-2 cleavage in this line. In in vivo experiments, xenografts of bcl-2–transfected PC12 cells were more susceptible to NCS toxicity than were xenografts of mock-transfected PC12 cells. Caspase 3-mediated Bcl-2 cleavage therefore plays an important role in the potentiation by Bcl-2 of NCS-induced apoptosis.