Linked Life Data

17885582

Source:http://linkedlifedata.com/resource/pubmed/id/17885582

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-9-21
pubmed:abstractText
Melanoma, the most deadly form of skin cancer, is very aggressive and resistant to present therapies. The transcription factor nuclear factor-kappa B (NF-kappaB) has been reported to be constitutively active in many types of cancer. Constitutively active NF-kappaB seen in melanoma likely plays a central role in cell survival and growth. We have established and characterized novel cell lines from our murine melanoma model. Here we report the constitutive activity of NF-kappaB in these melanoma-derived cells, as shown by electrophoretic mobility shift assay and reporter assays. We hypothesized that agents that inhibit NF-kappaB may also inhibit cell proliferation and may induce apoptosis in such melanoma cells. Curcumin has been shown to inhibit NF-kappaB activity in several cell types. In our system, curcumin selectively inhibited growth of melanoma cells, but not normal melanocytes. Curcumin induced melanoma cells to undergo apoptosis, as shown by caspase-3 activation, inversion of membrane phosphatidyl serine, and increases in cells in the sub-G1 phase. A curcumin dose-dependent inhibition of NF-kappaB-driven reporter activity correlated with decreased levels of phospho-IkappaBalpha, and decreased expression of NF-kappaB-target genes COX-2 and cyclin D1. This study demonstrates that the use of cells from our model system can facilitate studies of signaling pathways in melanoma. We furthermore conclude that curcumin, a natural and safe compound, inhibits NF-kappaB activity and the expression of its downstream target genes, and also selectively induces apoptosis of melanoma cells but not normal melanocytes. These encouraging in-vitro results support further investigation of curcumin for treatment of melanoma in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0960-8931
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
274-83
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17885582-Animals, pubmed-meshheading:17885582-Annexin A5, pubmed-meshheading:17885582-Antineoplastic Agents, pubmed-meshheading:17885582-Apoptosis, pubmed-meshheading:17885582-Caspase 3, pubmed-meshheading:17885582-Cell Proliferation, pubmed-meshheading:17885582-Cell Survival, pubmed-meshheading:17885582-Curcumin, pubmed-meshheading:17885582-Cyclin D, pubmed-meshheading:17885582-Cyclins, pubmed-meshheading:17885582-Cyclooxygenase 2, pubmed-meshheading:17885582-Down-Regulation, pubmed-meshheading:17885582-Electrophoretic Mobility Shift Assay, pubmed-meshheading:17885582-G1 Phase, pubmed-meshheading:17885582-Luciferases, pubmed-meshheading:17885582-Melanoma, Experimental, pubmed-meshheading:17885582-Mice, pubmed-meshheading:17885582-NF-kappa B, pubmed-meshheading:17885582-Skin Neoplasms, pubmed-meshheading:17885582-Tumor Cells, Cultured
pubmed:year
2007
pubmed:articleTitle
Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells.
pubmed:affiliation
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural