GUANG-YAW LIU2026-10-162026-10-162005-06-24Pure ID: 15086250Pure UUID: 143b1701-c593-4f84-a55b-f50bf43ccf7f10.1016/j.lfs.2005.01.010https://www.scopus.com/pages/publications/19444365828https://scholars.csmu.edu.tw/handle/123456789/31109Rottlerin is a widely selective protein kinase C delta (PKCδ) 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-G1 appearance, DNA fragmentation, loss of mitochondrial membrane potential (Δψm), release of mitochondrial cytochrome c into cytoplasm and proteolytic activation of caspase 9 and 3. Expression of PKCδ and Bcl-2 protein inhibited Δψm change and repressed cell death. These studies suggest that the cytotoxic effects of rottlerin through inhibition of PKCδ cause mitochondrial dysfunction, cytochrome c release from mitochondria into cytoplasm and the activation of caspases' cascade.13enjournal article