https://scholars.lib.ntu.edu.tw/handle/123456789/565273
Title: | An oral quinoline derivative, MPT0B392, causes leukemic cells mitotic arrest and overcomes drug resistant cancer cells | Authors: | Chao M.-W. Huang H.-L. HuangFu W.-C. Hsu K.-C. Liu Y.-M. Wu Y.-W. Lin C.-F. Chen Y.-L. Lai M.-J. Lee H.-Y. Liou J.P. Teng C.-M. CHIA-RON YANG |
Keywords: | Acute leukemia; Drug resistance; Mitotic arrest; MPT0B392 | Issue Date: | 2017 | Journal Volume: | 8 | Journal Issue: | 17 | Start page/Pages: | 27772-27785 | Source: | Oncotarget | Abstract: | Despite great advances in the treatment of acute leukemia, a renaissance of current chemotherapy needs to be improved. The present study elucidates the underlying mechanism of a new synthetic quinoline derivative, MPT0B392 (B392) against acute leukemia and its potential anticancer effect in drug resistant cells. B392 caused mitotic arrest and ultimately led to apoptosis. It was further demonstrated to be a novel microtubule-depolymerizing agent. The effects of oral administration of B392 showed relative potent anti-leukemia activity in an in vivo xenograft model. Further investigation revealed that B392 triggered induction of the mitotic arrest, followed by mitochondrial membrane potential loss and caspases cleavage by activation of c-Jun N-terminal kinase (JNK). In addition, B392 enhanced the cytotoxicity of sirolimus in sirolimusresistant acute leukemic cells through inhibition of Akt/mTOR pathway and Mcl-1 protein expression, and also was active in the p-glycoprotein (p-gp)-overexpressing National Cancer Institute/Adriamycin-Resistant cells with little susceptibility to p-gp. Taken together, B392 has potential as an oral mitotic drug and adjunct treatment for drug resistant cancer cells. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85018447814&doi=10.18632%2foncotarget.15115&partnerID=40&md5=0e6cddb4ba48879c9da53fff21534206 https://scholars.lib.ntu.edu.tw/handle/123456789/565273 |
ISSN: | 19492553 | DOI: | 10.18632/oncotarget.15115 | SDG/Keyword: | 6 methoxy 2 (3,4,5 trimethoxy benzenesulfonyl) quinolin 5 ylamine; antineoplastic agent; mammalian target of rapamycin; mitogen activated protein kinase; multidrug resistance protein; protein kinase B; protein mcl 1; rapamycin; stress activated protein kinase; synaptophysin; unclassified drug; vincristine; acute leukemia; animal experiment; animal model; animal tissue; antineoplastic activity; Article; cancer resistance; CCRF CEM cell line; cell cycle progression; concentration response; controlled study; cytotoxicity; down regulation; drug potentiation; enzyme activation; G2 phase cell cycle checkpoint; HL-60 cell line; human; human cell; immunohistochemistry; leukemia cell line; mitochondrial membrane potential; mitosis inhibition; MOLT 4 cell line; mouse; MTT assay; nonhuman; protein expression; staining; Western blotting |
Appears in Collections: | 藥學系 |
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