An oral quinoline derivative, MPT0B392, causes leukemic cells mitotic arrest and overcomes drug resistant cancer cells

Min Wu Chao, Han Li Huang, Wei Chun HuangFu, Kai Cheng Hsu, Yi Min Liu, Yi Wen Wu, Chao Feng Lin, Yi Lin Chen, Mei Jung Lai, Hsueh Yun Lee, Jing Ping Liou, Che Ming Teng, Chia Ron Yang

研究成果: 雜誌貢獻文章

3 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)27772-27785
頁數14
期刊Oncotarget
8
發行號17
DOIs
出版狀態已發佈 - 2017

ASJC Scopus subject areas

  • Oncology

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