https://scholars.lib.ntu.edu.tw/handle/123456789/564773
標題: | Zerumbone, a ginger sesquiterpene, induces apoptosis and autophagy in human hormone-refractory prostate cancers through tubulin binding and crosstalk between endoplasmic reticulum stress and mitochondrial insult | 作者: | Chan M.-L. Liang J.-W. LIH-CHING HSU Chang W.-L. SHOEI-SHENG LEE JIH-HWA GUH |
公開日期: | 2015 | 卷: | 388 | 期: | 11 | 起(迄)頁: | 1223-1236 | 來源出版物: | Naunyn-Schmiedeberg's Archives of Pharmacology | 摘要: | Zerumbone, a natural monocyclic sesquiterpene, is the main component of the tropical plant Zingiber zerumbet Smith. Zerumbone induced antiproliferative and apoptotic effects against PC-3 and DU-145, two human hormone-refractory prostate cancer (HRPC) cell lines. Zerumbone inhibited microtubule assembly and induced an increase of MPM-2 expression (specific recognition of mitotic proteins). It also caused an increase of phosphorylation of Bcl-2 and Bcl-xL, two key events in tubulin-binding effect, indicating tubulin-binding capability and mitotic arrest to zerumbone action. Furthermore, zerumbone induced several cellular effects distinct from tubulin-binding properties. First, zerumbone significantly increased, while paclitaxel (as a tubulin-binding control) decreased, Mcl-1 protein expression. Second, paclitaxel but not zerumbone induced Cdk1 activity. Third, zerumbone other than paclitaxel induced Cdc25C downregulation. The data suggest that, in addition to targeting tubulin/microtubule, zerumbone may act on other targets for signaling transduction. Zerumbone induced mitochondrial damage and endoplasmic reticulum (ER) stress as evidenced by the loss of mitochondrial membrane potential and upregulation of GRP-78 and CHOP/GADD153 expression. Zerumbone induced an increase of intracellular Ca2+ levels, a crosstalk marker between ER stress and mitochondrial insult, associated with the formation of active calpain I fragment. It induced apoptosis through a caspase-dependent way and caused autophagy as evidenced by dramatic LC3-II formation. In summary, the data suggest that zerumbone is a multiple targeting compound that inhibits tubulin assembly and induces a crosstalk between ER stress and mitochondrial insult, leading to apoptosis and autophagy in HRPCs. ? 2015 Springer-Verlag Berlin Heidelberg. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84945474085&doi=10.1007%2fs00210-015-1152-z&partnerID=40&md5=bb6d13bd9c39d34be20cdeb1643221d2 https://scholars.lib.ntu.edu.tw/handle/123456789/564773 |
ISSN: | 281298 | DOI: | 10.1007/s00210-015-1152-z | SDG/關鍵字: | calpain 1; caspase 3; caspase 7; caspase 9; cyclin A; cyclin B1; fodrin; glucose regulated protein 78; growth arrest and DNA damage inducible protein 153; histone H3; paclitaxel; protein bcl 2; protein bcl xl; protein mcl 1; thymidine; tubulin; zerumbone; apoptosis regulatory protein; calcium; cell cycle protein; sesquiterpene; tubulin; zerumbone; antiproliferative activity; apoptosis; Article; autophagy; castration resistant prostate cancer; cell cycle; cell cycle G1 phase; cell cycle S phase; cell death; cell differentiation; cell proliferation; chromatin structure; chromosome condensation; controlled study; down regulation; endoplasmic reticulum stress; G2 phase cell cycle checkpoint; histone acetylation; histone phosphorylation; human; human cell; immunofluorescence microscopy; male; microtubule assembly; mitochondrial membrane potential; mitosis inhibition; protein binding; protein expression; signal transduction; transcription initiation; upregulation; apoptosis; autophagy; castration resistant prostate cancer; drug effects; endoplasmic reticulum stress; ginger; metabolism; mitochondrial membrane potential; tumor cell line; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Calcium; Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; Endoplasmic Reticulum Stress; Ginger; Humans; Male; Membrane Potential, Mitochondrial; Prostatic Neoplasms, Castration-Resistant; Sesquiterpenes; Tubulin |
顯示於: | 藥學系 |
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