Linked Life Data

12584164

Source:http://linkedlifedata.com/resource/pubmed/id/12584164

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-2-13
pubmed:abstractText
Various naturally occurring flavonoids have been found to be cancer-protective in chemically induced animal cancer models and synthetic flavonoid derivatives are being tested for potential chemotherapeutic usefulness in clinical trials. This report demonstrates that human oral squamous carcinoma cells (SCC) are significantly more sensitive to growth inhibition by the naturally occurring flavonoid, morin (3,5,7,2',4'-pentahydroxyflavone) than normal oral mucosa (NOMC) (SCC IC(50) = 115 microM; NOMC IC(50) = 173 micro M; P for difference = 0.009). Structure/function comparisons indicate that both the 2' and 4' hydroxyl groups in morin are required for its tumour selectivity. Morin causes growth arrest in G(2)/M, without inducing apoptosis, and this is associated with induction of GADD45 and phosphorylation and inactivation of the cell cycle kinase, cdc2. Morin also has pleiotropic effects on kinase signalling pathways, including inhibition of activation of protein kinase B by mitogens (but not extracellular-regulated kinases 1/2) and activation of the stress pathway kinases, Jun N-terminal kinase and p38 kinase. p38 kinase activation is functionally important since inhibition of its activation by the specific inhibitor SB202190 partially prevented cell cycle arrest by morin. However, analysis of dose-response relationships reveals that the enhanced tumour sensitivity to morin may be explained by the fact that activation of AKT is inhibited at lower concentrations of morin in carcinomas than normal oral mucosa, whereas Jun N-terminal kinase, p38 kinase and GADD45 are all induced in parallel with the same dose-response curves in carcinomas and normal oral mucosa.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
171-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12584164-3T3 Cells, pubmed-meshheading:12584164-Animals, pubmed-meshheading:12584164-Blotting, Western, pubmed-meshheading:12584164-CHO Cells, pubmed-meshheading:12584164-Cell Division, pubmed-meshheading:12584164-Cricetinae, pubmed-meshheading:12584164-Enzyme Activation, pubmed-meshheading:12584164-Flavonoids, pubmed-meshheading:12584164-Humans, pubmed-meshheading:12584164-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:12584164-Mice, pubmed-meshheading:12584164-Mitogen-Activated Protein Kinases, pubmed-meshheading:12584164-Mouth Neoplasms, pubmed-meshheading:12584164-Protein-Serine-Threonine Kinases, pubmed-meshheading:12584164-Proto-Oncogene Proteins, pubmed-meshheading:12584164-Proto-Oncogene Proteins c-akt, pubmed-meshheading:12584164-Signal Transduction, pubmed-meshheading:12584164-Structure-Activity Relationship, pubmed-meshheading:12584164-Tumor Cells, Cultured, pubmed-meshheading:12584164-p38 Mitogen-Activated Protein Kinases
pubmed:year
2003
pubmed:articleTitle
Enhanced sensitivity of human oral tumours to the flavonol, morin, during cancer progression: involvement of the Akt and stress kinase pathways.
pubmed:affiliation
The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't