期刊
LIFE SCIENCES
卷 77, 期 6, 页码 707-719出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2005.01.010
关键词
Mallotus philippinensis; Euphorbiaceae; Rottlerin; apoptosis; mitochondrial membrane potential; cytochrome c; caspase
Rottlerin is a widely selective protein kinase C delta (PKC delta) inhibitor isolated from Mallotus philippinensis. It shown to be effective against several human tumor cell lines and in potentiating chemotherapy-induced cytotoxcicity. Using the trypan blue exclusion assay, we demonstrated that rottlerin reduced the viability in a dose- and time-dependent manner of human leukemia HL60 cells, human acute T cell leukemia Jurkat cells and mouse macrophage RAW 264.7 cells. Rottlerin caused apoptosis and the apaptotic processing was inhibited by a caspase inhibitor, z-VAD-fmk, in these haematopoietic cells. The apoptosis-inducing activities were determined by nuclear condensation, sub-G, appearance, DNA fragmentation, loss of mitochondrial membrane potential release of mitochondrial cytochrome c into cytoplasm and proteolytic activation of caspase 9 and 3. Expression of PKC delta and Bcl-2 protein inhibited Delta psi(m) change and repressed cell death. These studies suggest that the cytotoxic effects of rottlerin through inhibition Of PKC delta cause mitochondrial dysfunction, cytochrome c release from mitochondria into cytoplasm and the activation of caspases' cascade. (c) 2005 Elsevier Inc. All rights reserved.
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