Linked Life Data

19730790

Source:http://linkedlifedata.com/resource/pubmed/id/19730790

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-10-20
pubmed:abstractText
Aberrant activation of the Wnt/?-catenin signaling pathway promotes osteosarcoma tumorigenesis and metastasis. In this study, we tested the hypothesis that osteosarcoma progression may be delayed by disrupting the Wnt/?-catenin pathway using small molecule inhibitors such as curcumin and PKF118-310. Effective inhibitions of the Wnt/?-catenin pathway by curcumin and PKF118-310 in osteosarcoma cells were shown by the suppression of both intrinsic and activated ?-catenin/Tcf transcriptional activities using luciferase reporter assays. Western blot analysis revealed that there was no change in the amount of cytosolic ?-catenin, although nuclear ?-catenin was markedly reduced by treatment with either compounds. We next performed wound healing and Matrigel invasion assays and observed a dose-dependent decrease in osteosarcoma cell migration and invasion with curcumin and PKF118-310 treatment. Overexpression of the wild-type ?-catenin plasmid in osteosarcoma cells resulted in enhanced cell invasiveness but this effect was significantly overcome by curcumin. Gelatin zymography and Western blotting showed that reduced cell invasion with curcumin and PKF118-310 treatment correlated with the activity and protein level of matrix metalloproteinase-9 under conditions of intrinsic or extrinsic Wnt/?-catenin activation. Using cell apoptosis assay and cell cycle analysis, we further showed that the anti-proliferative effect of PKF118-310 is attributed to PKF118-310-induced apoptosis and G2/M phase arrest. Lastly, we observed that these anti-cancer effects correlated with the decreased expression of cyclin D1, c-Myc and survivin. Our findings strongly suggest that curcumin and PKF118-310 have great therapeutic potential for the treatment of osteosarcoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1573-0646
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
766-82
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:19730790-Antineoplastic Agents, pubmed-meshheading:19730790-Biological Agents, pubmed-meshheading:19730790-Cell Cycle, pubmed-meshheading:19730790-Cell Death, pubmed-meshheading:19730790-Cell Line, Tumor, pubmed-meshheading:19730790-Cell Movement, pubmed-meshheading:19730790-Cell Nucleus, pubmed-meshheading:19730790-Cell Proliferation, pubmed-meshheading:19730790-Cell Survival, pubmed-meshheading:19730790-Curcumin, pubmed-meshheading:19730790-Drug Screening Assays, Antitumor, pubmed-meshheading:19730790-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19730790-Humans, pubmed-meshheading:19730790-Matrix Metalloproteinase 9, pubmed-meshheading:19730790-Neoplasm Invasiveness, pubmed-meshheading:19730790-Osteosarcoma, pubmed-meshheading:19730790-Pyrimidinones, pubmed-meshheading:19730790-Signal Transduction, pubmed-meshheading:19730790-Triazines, pubmed-meshheading:19730790-Wnt Proteins, pubmed-meshheading:19730790-beta Catenin
pubmed:year
2010
pubmed:articleTitle
Antitumor activity of natural compounds, curcumin and PKF118-310, as Wnt/?-catenin antagonists against human osteosarcoma cells.
pubmed:affiliation
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't