pubmed-article:20463006 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C0023418 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C0031715 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C0600531 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C0243045 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C0041348 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C0376515 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C0314672 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C1444748 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C0237477 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
pubmed-article:20463006 | lifeskim:mentions | umls-concept:C1513354 | lld:lifeskim |
pubmed-article:20463006 | pubmed:issue | 2 | lld:pubmed |
pubmed-article:20463006 | pubmed:dateCreated | 2010-7-19 | lld:pubmed |
pubmed-article:20463006 | pubmed:abstractText | We investigated the signaling pathways associated with microtubule interaction and apoptosis in U937 cells in vitro and in the U937 xenograft model in vivo by using 6-pyrrolidinyl-2-(2-hydroxyphenyl)-4-quinazolinone (MJ-29). MJ-29 induced growth inhibition and cell death of leukemia cell lines (U937, HL-60, K562, and KG-1) in a dose- and time-dependent manner but did not obviously impair the viability of normal cells (peripheral blood mononuclear cells and human umbilical vein endothelial cells). MJ-29 interacted with alpha- and beta-tubulin, inhibited tubulin polymerization both in vitro and in vivo, and disrupted microtubule organization. MJ-29 caused mitotic arrest by activating cyclin-dependent kinase 1 (CDK1)/cyclin B complex activity. MJ-29-induced growth inhibition and activation of CDK1 activity were significantly attenuated by roscovitine (CDK inhibitor) and CDK1 small interfering RNA (siRNA). Furthermore, MJ-29-induced Bcl-2 phosphorylation was also significantly attenuated by CDK1 siRNA. MJ-29 caused an increase in the protein levels of cytosolic cytochrome c, apoptotic protease-activating factor-1, procaspase-9, and apoptosis-inducing factor. MJ-29-promoted activation of caspase-9 and caspase-3 during apoptosis was significantly attenuated by caspase-9 and caspase-3 inhibitors. It is noteworthy that in BALB/c(nu/nu) mice bearing U937 xenograft tumors MJ-29 inhibited tumor growth in vivo. The terminal deoxynucleotidyl transferase-mediated d-UTP nick end-labeling-positive apoptotic cells of tumor sections significantly increased in MJ-29-treated mice compared with the control group. In conclusion, our results suggest that MJ-29 induces mitotic arrest and apoptosis in U937 cells via CDK1-mediated Bcl-2 phosphorylation and inhibits the in vivo tumor growth of U937 xenograft mice. | lld:pubmed |
pubmed-article:20463006 | pubmed:language | eng | lld:pubmed |
pubmed-article:20463006 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20463006 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:20463006 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20463006 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20463006 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20463006 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20463006 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20463006 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20463006 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20463006 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:20463006 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:20463006 | pubmed:month | Aug | lld:pubmed |
pubmed-article:20463006 | pubmed:issn | 1521-0103 | lld:pubmed |
pubmed-article:20463006 | pubmed:author | pubmed-author:ChungJing-Gun... | lld:pubmed |
pubmed-article:20463006 | pubmed:author | pubmed-author:KuoSheng-ChuS... | lld:pubmed |
pubmed-article:20463006 | pubmed:author | pubmed-author:YangJai-SingJ... | lld:pubmed |
pubmed-article:20463006 | pubmed:author | pubmed-author:HourMann-JenM... | lld:pubmed |
pubmed-article:20463006 | pubmed:author | pubmed-author:HuangWen-WenW... | lld:pubmed |
pubmed-article:20463006 | pubmed:author | pubmed-author:LinKuei-LiKL | lld:pubmed |
pubmed-article:20463006 | pubmed:issnType | Electronic | lld:pubmed |
pubmed-article:20463006 | pubmed:volume | 334 | lld:pubmed |
pubmed-article:20463006 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:20463006 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:20463006 | pubmed:pagination | 477-88 | lld:pubmed |
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pubmed-article:20463006 | pubmed:year | 2010 | lld:pubmed |
pubmed-article:20463006 | pubmed:articleTitle | MJ-29 inhibits tubulin polymerization, induces mitotic arrest, and triggers apoptosis via cyclin-dependent kinase 1-mediated Bcl-2 phosphorylation in human leukemia U937 cells. | lld:pubmed |
pubmed-article:20463006 | pubmed:affiliation | Department of Pharmacology, China Medical University, Taichung, Taiwan. | lld:pubmed |
pubmed-article:20463006 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:20463006 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:20463006 | lld:pubmed |