Bcl-2 overexpression attenuates resveratrol-induced apoptosis in U937 cells by inhibition of caspase-3 activity.
Resveratrol has been shown to induce anti-proliferation and apoptosis of human cancer cell lines. In the present study, we determined the effect of high intracellular levels of the anti-apoptosis protein Bcl-2 on caspase-3 activation, PLC-gamma1 degradation and cytochrome c release during resveratrol-induced apoptosis. For this, we used U937/vector and U937/Bcl-2 cells, which were generated by transfection of the cDNA of the Bcl-2 gene. As compared with U937/vector, U937/Bcl-2 cells exhibited a 4-fold greater expression of Bcl-2. Treatment with 60 or 100 microM resveratrol for 24 h produced morphological features of apoptosis and DNA fragmentation in U937/vector cells, respectively. This was associated with caspase-3 activation and PLC-gamma1 degradation. In contrast, resveratrol-induced caspase-3 activation and PLC-gamma1 degradation and apoptosis were significantly inhibited in U937/Bcl-2 cells. Bcl-2 overexpressing cells exhibited less cytochrome c release and sustained expression levels of the IAP proteins during resveratrol-induced apoptosis. In addition, these findings indicate that Bcl-2 inhibits resveratrol-induced apoptosis by a mechanism that interferes with cytochrome c release and activity of caspase-3 that is involved in the execution of apoptosis.
Park
J W
JW
Department of Immunology, Department of Microbiology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu, Korea.
Choi
Y J
YJ
Suh
S I
SI
Baek
W K
WK
Suh
M H
MH
Jin
I N
IN
Min
D S
DS
Woo
J H
JH
Chang
J S
JS
Passaniti
A
A
Lee
Y H
YH
Kwon
T K
TK
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes / Q000378:metabolism; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D051966:Phospholipase C gamma; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D000077022:Survivin; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism; D020298:U937 Cells / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C107489:BIRC5 protein, human; D061945:Caspase Inhibitors; D002868:Chromosomal Proteins, Non-Histone; D016213:Cyclins; D003574:Cytochrome c Group; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D000077022:Survivin; D014764:Viral Proteins; D051028:bcl-2-Associated X Protein; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; D011065:Poly(ADP-ribose) Polymerases; D018844:Cyclin-Dependent Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077185:Resveratrol