کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9012778 | 1125014 | 2005 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The PKC delta inhibitor, rottlerin, induces apoptosis of haematopoietic cell lines through mitochondrial membrane depolarization and caspases' cascade
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
کاردیولوژی و پزشکی قلب و عروق
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چکیده انگلیسی
Rottlerin 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 (ÎÏm), release of mitochondrial cytochrome c into cytoplasm and proteolytic activation of caspase 9 and 3. Expression of PKCδ and Bcl-2 protein inhibited ÎÏm 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 77, Issue 6, 24 June 2005, Pages 707-719
Journal: Life Sciences - Volume 77, Issue 6, 24 June 2005, Pages 707-719
نویسندگان
Ya-Fan Liao, Ying-Cheng Hung, Wen-Huei Chang, Gregory J. Tsay, Tzyh-Chyuan Hour, Hui-Chih Hung, Guang-Yaw Liu,