https://scholars.lib.ntu.edu.tw/handle/123456789/569476
標題: | Investigation of extrinsic and intrinsic apoptosis pathways of new clerodane diterpenoids in human prostate cancer PC-3 cells | 作者: | Huang D.-M. Shen Y.-C. Wu C. Huang Y.-T. FAN-LU KUNG Teng C.-M. JIH-HWA GUH |
公開日期: | 2004 | 卷: | 503 | 期: | 44199 | 起(迄)頁: | 17-24 | 來源出版物: | European Journal of Pharmacology | 摘要: | In our continuing search to discover bioactive compounds from natural products, we isolated six new clerodane diterpenes, caseamembrins A to F, from Casearia membranacea and examined their antiproliferative activities in human hormone-resistant prostate cancer PC-3 cells. All of these compounds displayed effective antiproliferative activity using sulforhodamine B assays and induced cell apoptosis by a terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL)-reaction technique. The data demonstrated that caseamembrin C was the most effective compound among these clerodane diterpenoids. Caseamembrin C induced down-regulation of Bcl-2 and Bcl-xL expression, while up-regulation of proapoptotic protein Mcl-1S (short chain), suggesting that these Bcl-2 family member proteins may play a role on arbitrating the apoptotic cell death. Caseamembrin C also induced the up-regulation of Fas ligand (FasL) expression, cleavage and activation of caspase-8 and caspase-9, Bid cleavage and activation of executor caspase-3. However, z-IETD-FMK (Z-Ile-Glu-Thr-Asp-fluoromethyl ketone, a selective caspase-8 inhibitor) almost completely inhibited caseamembrin C-induced Bid cleavage without any modification of caspase-9 activation, indicating that the extrinsic pathway of FasL/caspase-8/Bid cascade only played a minor role in the apoptotic signaling. Taken together, it is suggested that caseamembrin C-induced apoptosis is predominantly through the activation of intrinsic apoptosis pathways by causing the down-regulation of Bcl-2 and Bcl-xL expression, up-regulation of Mcl-1S protein and activation of caspase-9 and caspase-3. ? 2004 Elsevier B.V. All rights reserved. |
URI: | 2-s2.0-7444265768 https://scholars.lib.ntu.edu.tw/handle/123456789/569476 |
ISSN: | 142999 | DOI: | 10.1016/j.ejphar.2004.09.040 | SDG/關鍵字: | benzyloxycarbonylisoleucylglutamylthreonylaspartyl fluoromethyl ketone; caseamembrin a; caseamembrin b; caseamembrin c; caseamembrin d; caseamembrin e; caseamembrin f; caspase 3; caspase 8; caspase 8 inhibitor; caspase 9; clerodane derivative; diterpenoid; FAS ligand; protein bcl 2; protein bcl x; protein Bid; protein mcl 1; sulforhodamine B; unclassified drug; antineoplastic activity; apoptosis; article; cancer cell culture; Casearia; Casearia membranacea; cell proliferation; controlled study; down regulation; drug mechanism; enzyme activation; enzyme degradation; human; human cell; nick end labeling; priority journal; prostate cancer; protein degradation; protein expression; protein family; Apoptosis; Blotting, Western; Caspases; Cell Line, Tumor; Cell Proliferation; Coloring Agents; Diterpenes; Diterpenes, Clerodane; Enzyme Activation; Fas Ligand Protein; Genes, bcl-2; Humans; In Situ Nick-End Labeling; Male; Membrane Glycoproteins; Neoplasm Proteins; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Rhodamines; Signal Transduction; Tetrazolium Salts; Thiazoles |
顯示於: | 藥學系 |
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