title: Bcl-2 overexpression attenuates resveratrol-induced apoptosis in U937 cells by inhibition of caspase-3 activity.
abstract: 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.
authors.affiliation: Department of Immunology, Department of Microbiology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu, Korea.
authors.forename: J W
authors.initials: JW
authors.lastname: Park
authors.forename: Y J
authors.initials: YJ
authors.lastname: Choi
authors.forename: S I
authors.initials: SI
authors.lastname: Suh
authors.forename: W K
authors.initials: WK
authors.lastname: Baek
authors.forename: M H
authors.initials: MH
authors.lastname: Suh
authors.forename: I N
authors.initials: IN
authors.lastname: Jin
authors.forename: D S
authors.initials: DS
authors.lastname: Min
authors.forename: J H
authors.initials: JH
authors.lastname: Woo
authors.forename: J S
authors.initials: JS
authors.lastname: Chang
authors.forename: A
authors.initials: A
authors.lastname: Passaniti
authors.forename: Y H
authors.initials: YH
authors.lastname: Lee
authors.forename: T K
authors.initials: TK
authors.lastname: Kwon
mesh_terms: 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
chemical_list: 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