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KMID : 0613820110210121678
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Journal of Life Science
2011 Volume.21 No. 12 p.1678 ~ p.1688
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Activation of Pro-Apoptotic Multidomain Bcl-2 Family Member Bak and Mitochondria-Dependent Caspase Cascade are Involved in p-Coumaric Acid-Induced Apoptosis in Human Jurkat T Cells
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Lee Je-Won
Kim Young-Ho
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Abstract
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The apoptogenic effect of p-coumaric acid, a phenolic acid found in various edible plants, on human acute leukemia Jurkat T cells was investigated. Exposure of Jurkat T cells to p-coumaric acid (50-150μM) caused cytotoxicity and TdT-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic DNA fragmentation along with Bak activation, △ψm loss, activation of caspase-9, -3, -7, and -8, and PARP degradation in a dose-dependent manner. However,these apoptotic events were completely abrogated in Jurkat T cells overexpressing Bcl-2.Under these conditions, necrosis was not accompanied. Pretreatment of the cells with the pan-caspase inhibitor (z-VAD-fmk) could prevent p-coumaric acid-induced sub-G₁ peak representing apoptotic cells, whereas it failed to block △ψm loss, indicating that the activation of caspase cascade was prerequisite for p-coumaric acid-induced apoptosis as a downstream event of △ψm loss. FADD- and caspase-8-positive wild-type Jurkat T cell clone A3, FADD-deficient Jurkat T cell clone I2.1, and caspase-8-deficient Jurkat T cell clone I9.2 exhibited similar susceptibilities to the cytotoxicity of p-coumaric acid, excluding an involvement of Fas/FasL system in triggering the apoptosis. The apoptogenic activity of p-coumaric acid is more potent in malignant Jurkat T cells than in normal human peripheral T cells. Together, these results demonstrated that p-coumaric acid-induced apoptogenic activity in Jurkat T cellswas mediated by Bak activation, △ψm loss, and subsequent activation of multiple caspases such as caspase-9, -3, -7, and-8, and PARP degradation, which could be regulated by anti-apoptotic protein Bcl-2.
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KEYWORD
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Apoptosis, cytotoxicity, p-coumaric acid, caspase cascade, leukemia Jurkat T cells, Bcl-2
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