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Article: Lupeol suppresses cisplatin-induced nuclear factor-κB activation in head and neck squamous cell carcinoma and inhibits local invasion and nodal metastasis in an orthotopic nude mouse model

TitleLupeol suppresses cisplatin-induced nuclear factor-κB activation in head and neck squamous cell carcinoma and inhibits local invasion and nodal metastasis in an orthotopic nude mouse model
Authors
Issue Date2007
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2007, v. 67 n. 18, p. 8800-8809 How to Cite?
AbstractA poor prognosis in head and neck squamous cell carcinoma (HNSCC) patients is commonly associated with the presence of regional metastasis. Cisplatin-based chemotherapy concurrent with radiation therapy is commonly used in the treatment of locally advanced HNSCC. However, the result is dismal due to common acquisition of chemoresistance and radioresistance. Epidemiologic studies have shown the importance of dietary substances in the prevention of HNSCC. Here, we found that lupeol, a triterpene found in fruits and vegetables, selectively induced substantial HNSCC cell death but exhibited only a minimal effect on a normal tongue fibroblast cell line in vitro. Down-regulation of NF-κB was identified as the major mechanism of the anticancer properties of lupeol against HNSCC. Lupeol alone was not only found to suppress tumor growth but also to impair HNSCC cell invasion by reversal of the NF-κB-dependent epithelial-to-mesenchymal transition. Lupeol exerted a synergistic effect with cisplatin, resulting in chemosensitization of HNSCC cell lines with high NF-κB activity in vitro. In in vivo studies, using an orthotopic metastatic nude mouse model of oral tongue squamous cell carcinoma, lupeol at a dose of 2 mg/animal dramatically decreased tumor volume and suppressed local metastasis, which was more effective than cisplatin alone. Lupeol exerted a significant synergistic cytotoxic effect when combined with low-dose cisplatin without side effects. Our results suggest that lupeol may be an effective agent either alone or in combination for treatment of advanced tumors. ©2007 American Association for Cancer Research.
Persistent Identifierhttp://hdl.handle.net/10722/148522
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLee, TKen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorWo, JYen_HK
dc.contributor.authorMa, Sen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorMyers, JNen_HK
dc.contributor.authorAltevogt, Pen_HK
dc.contributor.authorYuen, APWen_HK
dc.date.accessioned2012-05-29T06:13:29Z-
dc.date.available2012-05-29T06:13:29Z-
dc.date.issued2007en_HK
dc.identifier.citationCancer Research, 2007, v. 67 n. 18, p. 8800-8809en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148522-
dc.description.abstractA poor prognosis in head and neck squamous cell carcinoma (HNSCC) patients is commonly associated with the presence of regional metastasis. Cisplatin-based chemotherapy concurrent with radiation therapy is commonly used in the treatment of locally advanced HNSCC. However, the result is dismal due to common acquisition of chemoresistance and radioresistance. Epidemiologic studies have shown the importance of dietary substances in the prevention of HNSCC. Here, we found that lupeol, a triterpene found in fruits and vegetables, selectively induced substantial HNSCC cell death but exhibited only a minimal effect on a normal tongue fibroblast cell line in vitro. Down-regulation of NF-κB was identified as the major mechanism of the anticancer properties of lupeol against HNSCC. Lupeol alone was not only found to suppress tumor growth but also to impair HNSCC cell invasion by reversal of the NF-κB-dependent epithelial-to-mesenchymal transition. Lupeol exerted a synergistic effect with cisplatin, resulting in chemosensitization of HNSCC cell lines with high NF-κB activity in vitro. In in vivo studies, using an orthotopic metastatic nude mouse model of oral tongue squamous cell carcinoma, lupeol at a dose of 2 mg/animal dramatically decreased tumor volume and suppressed local metastasis, which was more effective than cisplatin alone. Lupeol exerted a significant synergistic cytotoxic effect when combined with low-dose cisplatin without side effects. Our results suggest that lupeol may be an effective agent either alone or in combination for treatment of advanced tumors. ©2007 American Association for Cancer Research.en_HK
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshAnimalsen_US
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols - Pharmacologyen_US
dc.subject.meshCarcinoma, Squamous Cell - Drug Therapy - Genetics - Metabolism - Pathologyen_US
dc.subject.meshCell Death - Drug Effectsen_US
dc.subject.meshCell Growth Processes - Drug Effectsen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Movement - Drug Effectsen_US
dc.subject.meshCisplatin - Administration & Dosage - Pharmacologyen_US
dc.subject.meshDown-Regulation - Drug Effectsen_US
dc.subject.meshDrug Synergismen_US
dc.subject.meshEpithelial Cells - Drug Effects - Pathologyen_US
dc.subject.meshHead And Neck Neoplasms - Drug Therapy - Genetics - Metabolism - Pathologyen_US
dc.subject.meshHumansen_US
dc.subject.meshI-Kappa B Kinase - Genetics - Metabolismen_US
dc.subject.meshLymphatic Metastasisen_US
dc.subject.meshMesoderm - Drug Effects - Pathologyen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Nudeen_US
dc.subject.meshNf-Kappa B - Antagonists & Inhibitors - Biosynthesis - Genetics - Metabolismen_US
dc.subject.meshNeoplasm Invasivenessen_US
dc.subject.meshPentacyclic Triterpenesen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTriterpenes - Administration & Dosage - Pharmacologyen_US
dc.subject.meshXenograft Model Antitumor Assaysen_US
dc.titleLupeol suppresses cisplatin-induced nuclear factor-κB activation in head and neck squamous cell carcinoma and inhibits local invasion and nodal metastasis in an orthotopic nude mouse modelen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, TK: tkwlee@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailMa, S: sma@pathology.hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.authorityLee, TK=rp00447en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityMa, S=rp00506en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1158/0008-5472.CAN-07-0801en_HK
dc.identifier.pmid17875721-
dc.identifier.scopuseid_2-s2.0-34548763142en_HK
dc.identifier.hkuros144438-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34548763142&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume67en_HK
dc.identifier.issue18en_HK
dc.identifier.spage8800en_HK
dc.identifier.epage8809en_HK
dc.identifier.eissn1538-7445-
dc.identifier.isiWOS:000249679500046-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLee, TK=7501439435en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridWo, JY=7003466728en_HK
dc.identifier.scopusauthoridMa, S=16444895800en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridMyers, JN=7402996499en_HK
dc.identifier.scopusauthoridAltevogt, P=7004626712en_HK
dc.identifier.scopusauthoridYuen, APW=7006290111en_HK
dc.identifier.citeulike5253830-

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