Source:http://linkedlifedata.com/resource/pubmed/id/11724334
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4A
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pubmed:dateCreated |
2001-11-28
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pubmed:abstractText |
The c-erbB-2 oncogene encodes a tyrosine kinase that constitutes the internal and transmembrane part of the epidermal growth factor receptor (EGFR). ErbB-2 overexpression has been reported in 20% to 30% of human adenocarcinomas of the breast and ovary, and has been linked to an unfavorable prognosis in patients. Hypericin is a protein tyrosine kinase inhibitor that has been exploited in models for anti-tumor and anti-viral activity. In this study, we investigated the effects of hypericin on the activity of the c-erbB-2 oncoprotein and its downstream kinases. We also investigated the effect of hypericin on metastasis. We used ovarian SK-OV-3 cells as a model to determine whether hypericin-induced cell death was associated with inhibition of c-erbB-2 expression and activation. The IC50 of hypericin after 72 hrs exposure was 7.5 microM as determined by the MTT assay. Apoptosis, which was assessed by morphological changes and a flow cytometric assay, was observed at 24 h after continuous exposure to 5 microM hypericin. Inhibition of expression of the c-erbB-2 protein was detected, using a monoclonal anti-erbB-2 antibody after 12-48 hrs of exposure to hypericin. Hypericin was found to inhibit autophosphorylation of the erbB-2 protein and downstream kinases such as MEK and ERK1/2. We also found up-regulation of p21WAF1 expression and down-regulation of Bcl-2 in hypericin treated cells. An invasion assay showed that hypericin inhibited the movement of SK-OV-3 cells into the Matrigel. However, gelatin zymography showed that hypericin had no effect on the secretion of matrix metalloproteinases (MMPs) in SK-OV-3 cells. From these results, we conclude that hypericin inhibits the growth of SK-OV-3 ovarian cancer cells, inhibits the autophosphorylation of c-erbB-2, induces apoptosis, and may inhibit invasion.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Perylene,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/hypericin
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pubmed:status |
MEDLINE
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pubmed:issn |
0250-7005
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2649-55
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11724334-Antineoplastic Agents,
pubmed-meshheading:11724334-Apoptosis,
pubmed-meshheading:11724334-Cell Division,
pubmed-meshheading:11724334-Cell Movement,
pubmed-meshheading:11724334-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:11724334-Cyclins,
pubmed-meshheading:11724334-Enzyme Inhibitors,
pubmed-meshheading:11724334-Female,
pubmed-meshheading:11724334-Humans,
pubmed-meshheading:11724334-Neoplasm Invasiveness,
pubmed-meshheading:11724334-Ovarian Neoplasms,
pubmed-meshheading:11724334-Perylene,
pubmed-meshheading:11724334-Protein-Tyrosine Kinases,
pubmed-meshheading:11724334-Receptor, erbB-2,
pubmed-meshheading:11724334-Signal Transduction,
pubmed-meshheading:11724334-Tumor Cells, Cultured
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pubmed:articleTitle |
Inhibition of c-erbB-2 expression an activity in human ovarian carcinoma cells by hypericin.
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pubmed:affiliation |
National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul. hyunsung@kfda.go.kr
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pubmed:publicationType |
Journal Article
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