Linked Life Data

18561312

Source:http://linkedlifedata.com/resource/pubmed/id/18561312

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-7-23
pubmed:abstractText
Glioblastoma Multiforme (GBM) is almost inevitably a fatal tumor of the brain with most individuals dying within 1 year of diagnosis. It is the most frequent brain tumor in adults. Dose-response studies showed that Cucurbitacin B inhibited 50% growth (ED(50)) of 5 human GBM cell lines in liquid culture at approximately 10(-7) M. Soft-gel assays demonstrated that nearly all of the GBM clonogenic cells were inhibited at 10(-8) M of Cucurbitacin B. FACS analysis found that the compound (10(-7) M, 24 hr) caused G2/M arrest. The GBM cells underwent profound morphologic changes within 15-30 min after exposure to Cucurbitacin B (10(-7) M), rounding up and losing their pseudopodia associated with disruption of actin and microtubules, as observed by immunoflourescence. Cucurbitacin B (10(-7) M) caused prominent multinucleation of the cells after they were pulse-exposed (48 hr) to the drug, washed and cultured in normal medium for an additional 2 days. The drug (10(-7) M, 3-24 hr) increased levels of p-p38, p-JNK and p-JUN in U87 and T98G GBM cell lines as seen by Western blot. Interestingly, alterations in cell morphology caused by Cucurbitacin B (10(-7) M) were blocked by the JNK inhibitor SP600125. In summary, Cucurbitacin B has a prominent anti-proliferative activity on GBM cells; and at least in part, the mode of action is by affecting the cytoskeleton, as well as, the JNK pathway. Clinical trails of this drug should be pursued in GBM.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1097-0215
pubmed:author
pubmed:copyrightInfo
Copyright 2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
123
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1364-75
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18561312-Antineoplastic Agents, Phytogenic, pubmed-meshheading:18561312-Apoptosis, pubmed-meshheading:18561312-Blotting, Western, pubmed-meshheading:18561312-Brain Neoplasms, pubmed-meshheading:18561312-Cell Line, Tumor, pubmed-meshheading:18561312-Cell Movement, pubmed-meshheading:18561312-Cell Proliferation, pubmed-meshheading:18561312-Cytoskeleton, pubmed-meshheading:18561312-Enzyme Inhibitors, pubmed-meshheading:18561312-Glioblastoma, pubmed-meshheading:18561312-Humans, pubmed-meshheading:18561312-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:18561312-Microscopy, Confocal, pubmed-meshheading:18561312-Phytotherapy, pubmed-meshheading:18561312-Plant Extracts, pubmed-meshheading:18561312-Proto-Oncogene Proteins c-jun, pubmed-meshheading:18561312-Trichosanthes, pubmed-meshheading:18561312-Triterpenes, pubmed-meshheading:18561312-p38 Mitogen-Activated Protein Kinases
pubmed:year
2008
pubmed:articleTitle
Cucurbitacin B markedly inhibits growth and rapidly affects the cytoskeleton in glioblastoma multiforme.
pubmed:affiliation
Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA. dong.yin@cshs.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural