Linked Life Data

20463006

Source:http://linkedlifedata.com/resource/pubmed/id/20463006

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-7-19
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
334
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
477-88
pubmed:meshHeading
pubmed-meshheading:20463006-Animals, pubmed-meshheading:20463006-Antineoplastic Agents, pubmed-meshheading:20463006-Apoptosis, pubmed-meshheading:20463006-Biopolymers, pubmed-meshheading:20463006-CDC2 Protein Kinase, pubmed-meshheading:20463006-Caspase 3, pubmed-meshheading:20463006-Caspase 9, pubmed-meshheading:20463006-Enzyme Induction, pubmed-meshheading:20463006-Humans, pubmed-meshheading:20463006-Male, pubmed-meshheading:20463006-Membrane Potential, Mitochondrial, pubmed-meshheading:20463006-Mice, pubmed-meshheading:20463006-Mice, Inbred BALB C, pubmed-meshheading:20463006-Mice, Nude, pubmed-meshheading:20463006-Mitosis, pubmed-meshheading:20463006-Neoplasm Transplantation, pubmed-meshheading:20463006-Phosphorylation, pubmed-meshheading:20463006-Pilot Projects, pubmed-meshheading:20463006-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:20463006-Signal Transduction, pubmed-meshheading:20463006-Transplantation, Heterologous, pubmed-meshheading:20463006-Tubulin, pubmed-meshheading:20463006-Tubulin Modulators, pubmed-meshheading:20463006-U937 Cells
pubmed:year
2010
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.
pubmed:affiliation
Department of Pharmacology, China Medical University, Taichung, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't