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Article: Lupeol targets liver tumor-initiating cells through phosphatase and tensin homolog modulation

TitleLupeol targets liver tumor-initiating cells through phosphatase and tensin homolog modulation
Authors
Issue Date2011
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2011, v. 53 n. 1, p. 160-170 How to Cite?
AbstractLiver 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-3β-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. © 2010 American Association for the Study of Liver Diseases.
Persistent Identifierhttp://hdl.handle.net/10722/148634
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 1/06C
HKU 7/CRF/09
Funding Information:

Supported by the Hong Kong Research Grants Council Collaborative Research Fund (HKU 1/06C and HKU 7/CRF/09). I. O. L. Ng is Loke Yew Professor in Pathology.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorLee, TKWen_US
dc.contributor.authorCastilho, Aen_US
dc.contributor.authorCheung, VCHen_US
dc.contributor.authorTang, KHen_US
dc.contributor.authorMa, Sen_US
dc.contributor.authorNg, IOLen_US
dc.date.accessioned2012-05-29T06:14:14Z-
dc.date.available2012-05-29T06:14:14Z-
dc.date.issued2011en_US
dc.identifier.citationHepatology, 2011, v. 53 n. 1, p. 160-170en_US
dc.identifier.issn0270-9139en_US
dc.identifier.urihttp://hdl.handle.net/10722/148634-
dc.description.abstractLiver 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-3β-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. © 2010 American Association for the Study of Liver Diseases.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_US
dc.relation.ispartofHepatologyen_US
dc.rightsHepatology. Copyright © John Wiley & Sons, Inc.-
dc.subject.meshAnimalsen_US
dc.subject.meshAntigens, Cden_US
dc.subject.meshCarcinoma, Hepatocellular - Drug Therapyen_US
dc.subject.meshCell Division - Drug Effectsen_US
dc.subject.meshDrug Resistance, Neoplasmen_US
dc.subject.meshGlycoproteinsen_US
dc.subject.meshHumansen_US
dc.subject.meshLiver Neoplasms - Drug Therapyen_US
dc.subject.meshMiceen_US
dc.subject.meshNeoplasm Transplantationen_US
dc.subject.meshPten Phosphohydrolase - Physiologyen_US
dc.subject.meshPentacyclic Triterpenes - Therapeutic Useen_US
dc.subject.meshPeptidesen_US
dc.titleLupeol targets liver tumor-initiating cells through phosphatase and tensin homolog modulationen_US
dc.typeArticleen_US
dc.identifier.emailLee, TKW:tkwlee@hkucc.hku.hken_US
dc.identifier.emailMa, S:sma@pathology.hku.hken_US
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_US
dc.identifier.authorityLee, TKW=rp00447en_US
dc.identifier.authorityMa, S=rp00506en_US
dc.identifier.authorityNg, IOL=rp00335en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1002/hep.24000en_US
dc.identifier.pmid20979057-
dc.identifier.scopuseid_2-s2.0-78751552761en_US
dc.identifier.hkuros189789-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78751552761&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume53en_US
dc.identifier.issue1en_US
dc.identifier.spage160en_US
dc.identifier.epage170en_US
dc.identifier.eissn1527-3350-
dc.identifier.isiWOS:000286406300018-
dc.publisher.placeUnited Statesen_US
dc.relation.projectMolecular pathology of liver cancer - a multidisciplinary study-
dc.relation.projectMolecular Pathology of Liver Cancer - a Multidisciplinary Study-

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