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標題: The PKC delta inhibitor, rottlerin, induces apoptosis of haematopoietic cell lines through mitochondrial membrane depolarization and caspases' cascade
作者: Liao, Y.F.
Hung, Y.C.
Chang, W.H.
Tsay, G.J.
Hour, T.C.
Hung, H.C.
Liu, G.Y.
關鍵字: Mallotus philippinensis;Euphorbiaceae;Rottlerin;apoptosis;mitochondrial membrane potential;cytochrome c;caspase;protein-kinase-c;activation;translocation;dysfunction;modulation;mechanism;release;bcl-2;bax
Project: Life Sciences
期刊/報告no:: Life Sciences, Volume 77, Issue 6, Page(s) 707-719.
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.
ISSN: 0024-3205
DOI: 10.1016/j.lfs.2005.01.010
Appears in Collections:生命科學系所

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