https://scholars.lib.ntu.edu.tw/handle/123456789/564790
標題: | Reevesioside A, a cardenolide glycoside, induces anticancer activity against human hormone-refractory prostate cancers through suppression of c-myc expression and induction of G1 arrest of the cell cycle | 作者: | Leu W.-J. Chang H.-S. Chan S.-H. Hsu J.-L. Yu C.-C. LIH-CHING HSU Chen I.-S. JIH-HWA GUH |
公開日期: | 2014 | 卷: | 9 | 期: | 1 | 起(迄)頁: | e87323 | 來源出版物: | PLoS ONE | 摘要: | In the past decade, there has been a profound increase in the number of studies revealing that cardenolide glycosides display inhibitory activity on the growth of human cancer cells. The use of potential cardenolide glycosides may be a worthwhile approach in anticancer research. Reevesioside A, a cardenolide glycoside isolated from the root of Reevesia formosana, displayed potent anti-proliferative activity against human hormone-refractory prostate cancers. A good correlation (r2 = 0.98) between the expression of Na +/K+ -ATPase α3 subunit and anti-proliferative activity suggested the critical role of the α3 subunit. Reevesioside A induced G1 arrest of the cell cycle and subsequent apoptosis in a thymidine block-mediated synchronization model. The data were supported by the down-regulation of several related cell cycle regulators, including cyclin D1, cyclin E and CDC25A. Reevesioside A also caused a profound decrease of RB phosphorylation, leading to an increased association between RB and E2F1 and the subsequent suppression of E2F1 activity. The protein and mRNA levels of c-myc, which can activate expression of many downstream cell cycle regulators, were dramatically inhibited by reevesioside A. Transient transfection of c-myc inhibited the down-regulation of both cyclin D1 and cyclin E protein expression to reevesioside A action, suggesting that c-myc functioned as an upstream regulator. Flow cytometric analysis of JC-1 staining demonstrated that reevesioside A also induced the significant loss of mitochondrial membrane potential. In summary, the data suggest that reevesioside A inhibits c-myc expression and downregulates the expression of CDC25A, cyclin D1 and cyclin E, leading to a profound decrease of RB phosphorylation. G1 arrest is, therefore, induced through E2F1 suppression. Consequently, reevesioside A causes mitochondrial damage and an ultimate apoptosis in human hormone-refractory prostate cancer cells. ? 2014 Leu et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84900325252&doi=10.1371%2fjournal.pone.0087323&partnerID=40&md5=bc9ce9bea5e5f7d017468bf483d03940 https://scholars.lib.ntu.edu.tw/handle/123456789/564790 |
ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0087323 | SDG/關鍵字: | cardenolide derivative; cell cycle protein 25; cyclin D1; cyclin E; membrane protein; Myc protein; reevesioside A; transcription factor E2F1; unclassified drug; antineoplastic activity; antiproliferative activity; apoptosis; article; calcium cell level; castration resistant prostate cancer; cell proliferation; controlled study; down regulation; drug inhibition; enzyme activity; enzyme repression; flow cytometry; G1 phase cell cycle checkpoint; human; human cell; medicinal plant; mitochondrial membrane potential; protein expression; protein function; protein phosphorylation; Reevesia formosana; staining; Analysis of Variance; Antineoplastic Agents; Blotting, Western; Calcium; Cardenolides; Cell Line, Tumor; Cell Proliferation; DNA Primers; Flow Cytometry; G1 Phase Cell Cycle Checkpoints; Gene Expression Regulation; Humans; Male; Membrane Potential, Mitochondrial; Prostatic Neoplasms, Castration-Resistant; Proto-Oncogene Proteins c-myc; Reverse Transcriptase Polymerase Chain Reaction |
顯示於: | 藥學系 |
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