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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-7-30
pubmed:abstractText
Because ErbB-2 receptor is involved in hormone-independency for growth and metastasis of prostate cancer cells, the aim was to investigate the effects of quercetin on ErbB-2 and ErbB-3 expression and its critical components such as MAP kinase and PI-3 kinase. Hemocytometric counts and [3H]-thymidine incorporation were used to determine the effects of quercetin, EGF and TGF-alpha on cell proliferation and DNA synthesis in PC-3 and LnCap cells. Changes in ErbB-2, ErbB-3 and components of MAPK and PI-3K pathways were analyzed by Western blot analysis. Treatment of PC-3 and LnCap cells with quercetin resulted in a dose-dependent growth inhibition. The rate of DNA synthesis was decreased by 40, 55 and 65% on treatment with 14.5, 29.0 and 58.0 microM of quercetin, respectively. Concomitantly, these treatments led to a dose-dependent decrease in ErbB-2, ErbB-3 and their basal autophosphorylation levels as compared to controls. Cyclin D1 expression and basal phosphorylation of c-Raf, MAPK, Elk-1 and Akt-1 in PC-3 cells was also inhibited by quercetin treatment. Co-treating PC-3 cells with quercetin significantly attenuated EGF- and TGF-alpha-induced growth and phosphorylation of ErbB-2, ErbB-3, c-Raf, MAPK kinase 1/2 (MEK1/2), MAPK, Elk-1 and Akt-1. Since ErbB receptor is important for growth, metastasis and drug resistance, inhibition of ErbB-2 and ErbB-3 by pharmacological doses of quercetin may provide a new approach for treatment of prostate cancers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
821-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12888923-Blotting, Western, pubmed-meshheading:12888923-Cell Division, pubmed-meshheading:12888923-Cell Line, Tumor, pubmed-meshheading:12888923-Cyclin D1, pubmed-meshheading:12888923-DNA, pubmed-meshheading:12888923-Dose-Response Relationship, Drug, pubmed-meshheading:12888923-Epidermal Growth Factor, pubmed-meshheading:12888923-Humans, pubmed-meshheading:12888923-MAP Kinase Signaling System, pubmed-meshheading:12888923-Male, pubmed-meshheading:12888923-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12888923-Phosphorylation, pubmed-meshheading:12888923-Prostatic Neoplasms, pubmed-meshheading:12888923-Proto-Oncogene Proteins c-raf, pubmed-meshheading:12888923-Quercetin, pubmed-meshheading:12888923-Receptor, erbB-2, pubmed-meshheading:12888923-Receptor, erbB-3, pubmed-meshheading:12888923-Transforming Growth Factor alpha
pubmed:year
2003
pubmed:articleTitle
Inhibition of ErbB-2 and ErbB-3 expression by quercetin prevents transforming growth factor alpha (TGF-alpha)- and epidermal growth factor (EGF)-induced human PC-3 prostate cancer cell proliferation.
pubmed:affiliation
Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre of Singapore, Singapore 169610, Republic of Singapore. cmrhth@nccs.com.sg
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't