https://scholars.lib.ntu.edu.tw/handle/123456789/543841
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Leu W.-J. | en_US |
dc.contributor.author | Swain S.P. | en_US |
dc.contributor.author | Chan S.-H. | en_US |
dc.contributor.author | Hsu J.-L. | en_US |
dc.contributor.author | SHIH-PING LIU | en_US |
dc.contributor.author | Chan M.-L. | en_US |
dc.contributor.author | Yu C.-C. | en_US |
dc.contributor.author | LIH-CHING HSU | en_US |
dc.contributor.author | Chou Y.-L. | en_US |
dc.contributor.author | Chang W.-L. | en_US |
dc.contributor.author | Hou D.-R. | en_US |
dc.contributor.author | JIH-HWA GUH | en_US |
dc.creator | Leu W.-J.;Swain S.P.;Chan S.-H.;Hsu J.-L.;Shih-Ping Liu;Chan M.-L.;Yu C.-C.;Hsu L.-C.;Chou Y.-L.;Chang W.-L.;Hou D.-R.;Guh J.-H. | - |
dc.date.accessioned | 2021-01-29T03:17:17Z | - |
dc.date.available | 2021-01-29T03:17:17Z | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84998922422&doi=10.18632%2foncotarget.12765&partnerID=40&md5=0d4316cb1013f7404aba2bd42bce78aa | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/543841 | - |
dc.description.abstract | A series of triazole-based small molecules that mimic FTY720-mediated anticancer activity but minimize its immunosuppressive effect have been produced. SPS-7 is the most effective derivative displaying higher activity than FTY720 in anti-proliferation against human hormone-refractory prostate cancer (HRPC). It induced G1 arrest of cell cycle and subsequent apoptosis in thymidine blockmediated synchronization model. The data were supported by a decrease of cyclin D1 expression, a dramatic increase of p21 expression and an associated decrease in RB phosphorylation. c-Myc overexpression replenished protein levels of cyclin D1 indicating that c-Myc was responsible for cell cycle regulation. PI3K/Akt/mTOR signaling pathways through p70S6K- and 4EBP1-mediated translational regulation are critical to cell proliferation and survival. SPS-7 significantly inhibited this translational pathway. Overexpression of Myr-Akt (constitutively active Akt) completely abolished SPS-7-induced inhibitory effect on mTOR/p70S6K/4EBP1 signaling and c-Myc protein expression, suggesting that PI3K/Akt serves as a key upstream regulator. SPS-7 also demonstrated substantial anti-tumor efficacy in an in vivo xenograft study using PC-3 mouse model. Notably, FTY720 but not SPS-7 induced a significant immunosuppressive effect as evidenced by depletion of marginal zone B cells, downregulation of sphingosine-1-phosphate receptors and a decrease in peripheral blood lymphocytes. In conclusion, the data suggest that SPS-7 is not an immunosuppressant while induces anticancer effect against HRPC through inhibition of Akt/mTOR/ p70S6K pathwaysthat down-regulate protein levels of both c-Myc and cyclin D1, leading to G1 arrest of cell cycle and subsequent apoptosis. The data also indicate the potential of SPS-7 since PI3K/Akt signalingis responsive for the genomic alterations in prostate cancer. | - |
dc.publisher | Impact Journals LLC | - |
dc.relation.ispartof | Oncotarget | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | 1,3 dihydroxy 2 [(1 octadecyl 1h 1,2,3 triazol 4 yl)methyl]propan 2 aminium chloride; cyclin D1; fingolimod; initiation factor 4E binding protein 1; mammalian target of rapamycin; Myc protein; phosphatidylinositol 3 kinase; protein kinase B; S6 kinase; sphingosine 1 phosphate receptor; triazole derivative; unclassified drug; antineoplastic agent; fingolimod; MTOR protein, human; Myc protein; MYC protein, human; phosphatidylinositol 3 kinase; protein kinase B; target of rapamycin kinase; triazole derivative; animal experiment; animal model; animal tissue; antineoplastic activity; antiproliferative activity; apoptosis; Article; autophagy; B lymphocyte; cancer inhibition; castration resistant prostate cancer; cell cycle regulation; cell proliferation; cell survival; controlled study; drug cytotoxicity; drug efficacy; drug selectivity; drug synthesis; G1 phase cell cycle checkpoint; human; human cell; human tissue; IC50; immunomodulation; in vitro study; in vivo study; lymphocyte homing; male; mitochondrial membrane potential; mouse; nonhuman; peripheral lymphocyte; prostate cancer cell line; protein expression; receptor down regulation; signal transduction; structure activity relation; translation regulation; tumor xenograft; administration and dosage; animal; castration resistant prostate cancer; cell cycle; chemistry; drug effects; drug screening; gene expression regulation; metabolism; molecular library; pharmacology; signal transduction; tumor cell line; Animals; Antineoplastic Agents; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Fingolimod Hydrochloride; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Phosphatidylinositol 3-Kinases; Prostatic Neoplasms, Castration-Resistant; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Signal Transduction; Small Molecule Libraries; TOR Serine-Threonine Kinases; Triazoles; Xenograft Model Antitumor Assays | - |
dc.title | Non-immunosuppressive triazole-based small molecule induces anticancer activity against human hormone-refractory prostate cancers: The role in inhibition of PI3K/AKT/mTOR and c-Myc signaling pathways | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.18632/oncotarget.12765 | - |
dc.identifier.pmid | 27769069 | - |
dc.identifier.scopus | 2-s2.0-84998922422 | - |
dc.relation.pages | 76995-77009 | - |
dc.relation.journalvolume | 7 | - |
dc.relation.journalissue | 47 | - |
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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