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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Blotting, Western
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Caspase 3
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Caspase Inhibitors*
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Caspases / metabolism
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Cell Cycle / drug effects
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Chromosomal Proteins, Non-Histone / metabolism
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Cyclin-Dependent Kinases / metabolism
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Cyclins / metabolism
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Cytochrome c Group / metabolism
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Flow Cytometry
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Humans
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Inhibitor of Apoptosis Proteins
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Isoenzymes / metabolism
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Microtubule-Associated Proteins*
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Neoplasm Proteins
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Phospholipase C gamma
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Poly(ADP-ribose) Polymerases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Resveratrol
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Stilbenes / pharmacology*
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Survivin
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Transfection
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Type C Phospholipases / metabolism
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U937 Cells / metabolism*
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Viral Proteins / metabolism
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bcl-2-Associated X Protein
Substances
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BIRC5 protein, human
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Caspase Inhibitors
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Chromosomal Proteins, Non-Histone
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Cyclins
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Cytochrome c Group
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Inhibitor of Apoptosis Proteins
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Isoenzymes
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Microtubule-Associated Proteins
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Neoplasm Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Stilbenes
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Survivin
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Viral Proteins
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bcl-2-Associated X Protein
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inhibitor of apoptosis, Nucleopolyhedrovirus
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Poly(ADP-ribose) Polymerases
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Cyclin-Dependent Kinases
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Type C Phospholipases
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Phospholipase C gamma
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CASP3 protein, human
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Caspase 3
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Caspases
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Resveratrol