Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-11-17
pubmed:abstractText
Roscovitine has been reported to have anti-tumor effects in some cancer cell lines. The phosphatidylinositol-3-kinase (PI3K) signaling, which activates protein kinase B (PKB)/Akt, is known to mediate cell survival. The current study examined the role of wortmannin, a PI3K inhibitor, as a chemosensitizer for roscovitine and its proposed mechanism of action. The results showed that wortmannin significantly chemosensitized three human tumor cell lines (A549, HCT116 and HeLa cells). In A549 cells, wortmannin increased roscovitine-induced apoptosis in a dose-dependent manner, which was correlated with the inhibition of phosphorylated PKB/Akt level. Wortmannin enhanced the effects of roscovitine by causing pronounced reduction of mitochondrial transmembrane potential (MMP) and increases of cytochrome c release and active caspase-3, as well as enhanced activation of Bax and Bad, including Bax oligomerization and mitochondrial translocation of Bax and Bad. Taken together, these results provide evidence for the potential application of roscovitine/wormannin combination in clinical treatment for solid tumors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/BAD protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Purines, http://linkedlifedata.com/resource/pubmed/chemical/Quinolines, http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein, http://linkedlifedata.com/resource/pubmed/chemical/bcl-Associated Death Protein, http://linkedlifedata.com/resource/pubmed/chemical/roscovitine, http://linkedlifedata.com/resource/pubmed/chemical/waltherione-A, http://linkedlifedata.com/resource/pubmed/chemical/waltherione-B
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1872-7980
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
232-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19541408-Antineoplastic Agents, pubmed-meshheading:19541408-Apoptosis, pubmed-meshheading:19541408-Blotting, Western, pubmed-meshheading:19541408-Caspase 3, pubmed-meshheading:19541408-Cell Line, Tumor, pubmed-meshheading:19541408-Cell Proliferation, pubmed-meshheading:19541408-Cell Survival, pubmed-meshheading:19541408-Dose-Response Relationship, Drug, pubmed-meshheading:19541408-Drug Synergism, pubmed-meshheading:19541408-Flow Cytometry, pubmed-meshheading:19541408-HCT116 Cells, pubmed-meshheading:19541408-HeLa Cells, pubmed-meshheading:19541408-Humans, pubmed-meshheading:19541408-Membrane Potential, Mitochondrial, pubmed-meshheading:19541408-Phosphatidylinositol 3-Kinases, pubmed-meshheading:19541408-Protein Transport, pubmed-meshheading:19541408-Proto-Oncogene Proteins c-akt, pubmed-meshheading:19541408-Purines, pubmed-meshheading:19541408-Quinolines, pubmed-meshheading:19541408-Signal Transduction, pubmed-meshheading:19541408-bcl-2-Associated X Protein, pubmed-meshheading:19541408-bcl-Associated Death Protein
pubmed:year
2009
pubmed:articleTitle
Wortmannin potentiates roscovitine-induced growth inhibition in human solid tumor cells by repressing PI3K/Akt pathway.
pubmed:affiliation
Department of Pharmacology, The Fourth Military Medical University, Xi'an 710032, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't