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 (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

指紋

Leukemia
Pharmaceutical Preparations
Neoplasms
Glycoproteins
National Cancer Institute (U.S.)
JNK Mitogen-Activated Protein Kinases
Mitochondrial Membrane Potential
Sirolimus
Caspases
Heterografts
Microtubules
Doxorubicin
Oral Administration
Apoptosis
Drug Therapy
quinoline
Therapeutics
Proteins
Renaissance

ASJC Scopus subject areas

  • Oncology

引用此文

An oral quinoline derivative, MPT0B392, causes leukemic cells mitotic arrest and overcomes drug resistant cancer cells. / Chao, Min Wu; Huang, Han Li; HuangFu, Wei Chun; Hsu, Kai Cheng; Liu, Yi Min; Wu, Yi Wen; Lin, Chao Feng; Chen, Yi Lin; Lai, Mei Jung; Lee, Hsueh Yun; Liou, Jing Ping; Teng, Che Ming; Yang, Chia Ron.

於: Oncotarget, 卷 8, 編號 17, 2017, p. 27772-27785.

研究成果: 雜誌貢獻文章

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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.",
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T1 - An oral quinoline derivative, MPT0B392, causes leukemic cells mitotic arrest and overcomes drug resistant cancer cells

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AU - Huang, Han Li

AU - HuangFu, Wei Chun

AU - Hsu, Kai Cheng

AU - Liu, Yi Min

AU - Wu, Yi Wen

AU - Lin, Chao Feng

AU - Chen, Yi Lin

AU - Lai, Mei Jung

AU - Lee, Hsueh Yun

AU - Liou, Jing Ping

AU - Teng, Che Ming

AU - Yang, Chia Ron

PY - 2017

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N2 - 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.

AB - 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.

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