Source:http://linkedlifedata.com/resource/pubmed/id/20979057
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2011-1-21
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pubmed:abstractText |
Liver tumor-initiating cells (T-ICs) are capable of self-renewal and tumor initiation and are more chemoresistant to chemotherapeutic drugs. The current therapeutic strategies for targeting stem cell self-renewal pathways therefore represent rational approaches for cancer prevention and treatment. In the present study, we found that Lup-20(29)-en-3?-ol (lupeol), a triterpene found in fruits and vegetables, inhibited the self-renewal ability of liver T-ICs present in both hepatocellular carcinoma (HCC) cell lines and clinical HCC samples, as reflected by hepatosphere formation. Furthermore, lupeol inhibited in vivo tumorigenicity in nude mice and down-regulated CD133 expression, which was previously shown to be a T-IC marker for HCC. In addition, lupeol sensitized HCC cells to chemotherapeutic agents through the phosphatase and tensin homolog (PTEN)-Akt-ABCG2 pathway. PTEN plays a crucial role in the self-renewal and chemoresistance of liver T-ICs; down-regulation of PTEN by a lentiviral-based approach reversed the effect of lupeol on liver T-ICs. Using an in vivo chemoresistant HCC tumor model, lupeol dramatically decreased the tumor volumes of MHCC-LM3 HCC cell line-derived xenografts, and the effect was equivalent to that of combined cisplatin and doxorubicin treatment. Lupeol exerted a synergistic effect without any adverse effects on body weight when combined with chemotherapeutic drugs. CONCLUSION: Our results suggest that lupeol may be an effective dietary phytochemical that targets liver T-ICs.
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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/AC133 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/Pentacyclic Triterpenes,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Pten protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/lupeol
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1527-3350
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pubmed:author | |
pubmed:copyrightInfo |
Copyright © 2010 American Association for the Study of Liver Diseases.
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pubmed:issnType |
Electronic
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
160-70
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pubmed:meshHeading |
pubmed-meshheading:20979057-Animals,
pubmed-meshheading:20979057-Antigens, CD,
pubmed-meshheading:20979057-Carcinoma, Hepatocellular,
pubmed-meshheading:20979057-Cell Division,
pubmed-meshheading:20979057-Drug Resistance, Neoplasm,
pubmed-meshheading:20979057-Glycoproteins,
pubmed-meshheading:20979057-Humans,
pubmed-meshheading:20979057-Liver Neoplasms,
pubmed-meshheading:20979057-Mice,
pubmed-meshheading:20979057-Neoplasm Transplantation,
pubmed-meshheading:20979057-PTEN Phosphohydrolase,
pubmed-meshheading:20979057-Pentacyclic Triterpenes,
pubmed-meshheading:20979057-Peptides
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pubmed:year |
2011
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pubmed:articleTitle |
Lupeol targets liver tumor-initiating cells through phosphatase and tensin homolog modulation.
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pubmed:affiliation |
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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