https://scholars.lib.ntu.edu.tw/handle/123456789/543863
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Hsu J.-L. | en_US |
dc.contributor.author | SHIH-PING LIU | en_US |
dc.contributor.author | Lee C.-C. | en_US |
dc.contributor.author | LIH-CHING HSU | en_US |
dc.contributor.author | Ho Y.-F. | en_US |
dc.contributor.author | Huang H.-S. | en_US |
dc.contributor.author | JIH-HWA GUH | en_US |
dc.creator | Hsu J.-L.;Shih-Ping Liu;Lee C.-C.;Hsu L.-C.;Ho Y.-F.;Huang H.-S.;Guh J.-H. | - |
dc.date.accessioned | 2021-01-29T03:17:24Z | - |
dc.date.available | 2021-01-29T03:17:24Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 0028-1298 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84930885034&doi=10.1007%2fs00210-014-0998-9&partnerID=40&md5=f4f462a2d53b3b8bd622e66ed036d6c5 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/543863 | - |
dc.description.abstract | Hormone-refractory metastatic prostate cancer (HRMPC), which is metastatic and resistant to hormone therapy, is an intractable problem in clinical treatment. Anthraquinone-based natural products and synthetic compounds have shown anticancer activity. However, cardiac toxicity is a major adverse reaction in these compounds. CC-36, a unique anthraquinone derivative, displayed higher antiproliferative activity in HRMPC than that in H9c2 cardiomyoblasts and normal prostate cells with the selectivity of five and twelve times, respectively. CC-36 caused G1 arrest of the cell cycle associated with an upregulation of p21 and downregulated levels of cyclin D1 and cyclin E expressions. Immunoprecipitation assay and Western blotting analysis showed that CC-36 triggered an increase of TSC1/TSC2 association and suppressed the phosphorylation of mammalian target of rapamycin (mTOR) (Ser2448) and p70 ribosomal protein S6 kinase (p70S6K) (Thr389), indicating the inhibition of both kinases' activities. CC-36 induced liver kinase B1 (LKB1) phosphorylation at Thr189, leading to LKB1 translocation from nucleus to cytosol for AMPKα phosphorylation (Thr172) and the kinase activation. The signaling pathway was validated using small interfering RNA (siRNA) technique with LKB1 knockdown. The combination treatment of MK2206 (a specific Akt inhibitor) with CC-36 showed a synergistic apoptosis in PC-3 cells indicating a potential combination strategy for LKB1 activators. Taken together, the data suggest that CC-36 displays anti-HRMPC activity through the activation of LKB1-AMPK pathway, leading to an inhibition of mTOR signaling and the induction of G1 arrest of the cell cycle. The combination use of Akt inhibitors with agents acting through LKB1-AMPK-mTOR pathway is a potential strategy for HRMPC treatment. ? 2014 Springer-Verlag Berlin Heidelberg. | - |
dc.publisher | Springer Verlag | - |
dc.relation.ispartof | Naunyn-Schmiedeberg's Archives of Pharmacology | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | anthraquinone derivative; hydroxymethylglutaryl coenzyme A reductase kinase; MTOR protein, human; protein serine threonine kinase; STK11 protein, human; target of rapamycin kinase; antagonists and inhibitors; cell proliferation; chemistry; dose response; drug effects; heart muscle cell; human; male; metabolism; physiology; Prostatic Neoplasms, Castration-Resistant; signal transduction; tumor cell line; AMP-Activated Protein Kinases; Anthraquinones; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Humans; Male; Myocytes, Cardiac; Prostatic Neoplasms, Castration-Resistant; Protein-Serine-Threonine Kinases; Signal Transduction; TOR Serine-Threonine Kinases | - |
dc.title | A unique amidoanthraquinone derivative displays antiproliferative activity against human hormone-refractory metastatic prostate cancers through activation of LKB1-AMPK-mTOR signaling pathway | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1007/s00210-014-0998-9 | - |
dc.identifier.pmid | 25005758 | - |
dc.identifier.scopus | 2-s2.0-84930885034 | - |
dc.relation.pages | 979-990 | - |
dc.relation.journalvolume | 387 | - |
dc.relation.journalissue | 10 | - |
item.openairetype | journal article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
item.grantfulltext | none | - |
crisitem.author.dept | Urology-NTUH | - |
crisitem.author.dept | Urology | - |
crisitem.author.dept | Pharmacy | - |
crisitem.author.dept | School of Pharmacy | - |
crisitem.author.dept | Pharmacy | - |
crisitem.author.dept | School of Pharmacy | - |
crisitem.author.orcid | 0000-0002-8015-0695 | - |
crisitem.author.orcid | 0000-0002-7816-3825 | - |
crisitem.author.orcid | 0000-0002-6738-6054 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 醫學系 |
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