Source:http://linkedlifedata.com/resource/pubmed/id/18089718
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12 Pt 1
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pubmed:dateCreated |
2007-12-19
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pubmed:abstractText |
Effective strategies are lacking for the management of urinary bladder cancer for which smoking is a potential risk factor. Herein, we evaluated chemoprevention of urinary bladder cancer by natural chemopreventive agents, silymarin and silibinin, in a preclinical animal (ICR mouse) model of bladder cancer induced by tobacco smoke carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN). Mice were fed p.o. with saline or OH-BBN (0.05%, w/v) in drinking water for 6 weeks or with silymarin or silibinin (200 mg/kg body weight for both) starting 1 week before OH-BBN exposure for 51 weeks. Silymarin and silibinin strongly arrested OH-BBN-induced tumor progression at the stage of mucosal dysplasia with a striking reduction in papillary nodular dysplasia as well as invasive carcinoma. Some silymarin- or silibinin-treated mice developed no urothelial lesions in spite of OH-BBN exposure. Immunohistochemical analyses at study conclusion revealed that silymarin and silibinin decreased cell proliferation by 42% (P < 0.001) and 44% (P < 0.001) and increased apoptosis by 4-fold (P < 0.05) and 6-fold (P < 0.05) in OH-BBN-induced urothelium, respectively. Antiproliferative and apoptotic effects of silymarin and silibinin were associated with decreases in (a) cyclin D1 protein level and extracellular signal-regulated kinase-1/2 phosphorylation and in (b) protein levels of survivin and nuclear phospho-p65 (Ser(276) and Ser(536)), respectively. Together, these results suggest that silymarin and silibinin inhibit chemically induced urinary bladder tumor growth and progression possibly by inhibiting cell proliferation and enhancing apoptosis.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anticarcinogenic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Butylhydroxybutylnitrosamine,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Silymarin,
http://linkedlifedata.com/resource/pubmed/chemical/silybin
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1535-7163
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3248-55
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18089718-Animals,
pubmed-meshheading:18089718-Anticarcinogenic Agents,
pubmed-meshheading:18089718-Apoptosis,
pubmed-meshheading:18089718-Butylhydroxybutylnitrosamine,
pubmed-meshheading:18089718-Carcinogens,
pubmed-meshheading:18089718-Cell Proliferation,
pubmed-meshheading:18089718-Cyclin D1,
pubmed-meshheading:18089718-Male,
pubmed-meshheading:18089718-Mice,
pubmed-meshheading:18089718-Mice, Inbred ICR,
pubmed-meshheading:18089718-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:18089718-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:18089718-NF-kappa B,
pubmed-meshheading:18089718-Phosphorylation,
pubmed-meshheading:18089718-Silymarin,
pubmed-meshheading:18089718-Urinary Bladder Neoplasms
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pubmed:year |
2007
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pubmed:articleTitle |
Chemopreventive effects of silymarin and silibinin on N-butyl-N-(4-hydroxybutyl) nitrosamine induced urinary bladder carcinogenesis in male ICR mice.
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pubmed:affiliation |
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Box C238, Denver, CO 80262, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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