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KMID : 0545120020120060950
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Journal of Microbiology and Biotechnology
2002 Volume.12 No. 6 p.950 ~ p.956
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Apoptotic Activity of Insect Pathogenic Fungus Paecilomyces japonica Toward Human Acute Leukemia Jurkat T Cells is Associated with Mitochondria-Dependent Caspase-3 Activation Regulated by Bcl-2
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PARK, HYE WON
JUN, DO YOUN/KIM, YOUNG HO
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Abstract
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The antitumor activity of the insect pathogenic fungus Paecilomyces japonica has been attributed to apoptotic cell death. However, the mechanism underlying the induced apoptosis has not yet been elucidated. In this study, we for the first time show that mitochondria-dependent capase-3 activation was associated with the apoptotic activity of P. japonica in human acute leukemia Jurkat T cells. When Jurkat T cells were treated with the ethyl acetate extract of P. japonica at concentrations ranging from 2-6 ㎍/ml, appototic cell death, accompanied by several biochemical events such as capase-9 activation, capase-3 activation, degradation of poly (ADP-ribose) polymerase (PARP), and apoptotic DNA fragmentation, was included in a dose-dependent manner. In addition, the release of cytochrome c from mitochondria was detected. Under these conditions, the expression of Fas and Fas-ligand (FasL) remained unchanged. Ethyl acetate extract-induced mitochondrial cytochrome c release, capase-3 activation, PARP cleavage, and apoptotic DNA fragmentation were suppressed by the ectopic expression of Bcl-1, which is known to block mitochondrial cytochrome c release. Accordingly, these results demonstrate that P. japonica-included apoptotic cell death is mediated by a cytochrome c-dependent capase-3 activation pathway that can be interrupted by Bcl-2.
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