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Article: Cucurbitacin I elicits anoikis sensitization, inhibits cellular invasion and in vivo tumor formation ability of nasopharyngeal carcinoma cells

TitleCucurbitacin I elicits anoikis sensitization, inhibits cellular invasion and in vivo tumor formation ability of nasopharyngeal carcinoma cells
Authors
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2009, v. 30 n. 12, p. 2085-2094 How to Cite?
AbstractNasopharyngeal carcinoma (NPC) is an Asian-prevalent head and neck cancer with high invasiveness. Although several important risk factors for NPC development have been identified, there is currently no preventive strategy for NPC, even in endemic regions. Signal transducer and activator of transcription 3 (STAT3) has been implicated in NPC carcinogenesis, which may serve as a potential target for cancer prevention. Here, we examined the chemopreventive potential of Cucurbitacin I, a natural-occurring selective inhibitor of JAK/STAT3, in NPC models. We hypothesized that Cucurbitacin I would prevent NPC invasion and tumor formation. Our data demonstrated that brief exposure of NPC cells to Cucurbitacin I was sufficient to significantly reduce the in vitro clonogenicity and in vivo tumorigenicity of NPC cells. The chemopreventive potential of Cucurbitacin I was further demonstrated by pre-dosing of the animals with Cucurbitacin I prior to tumor inoculation, which was found to be able to suppress tumor growth up to 7 days post-inoculation. The anti-proliferation activity of Cucurbitacin I was accompanied by downregulation of phospho-STAT3 and STAT3 target gene expression (e.g. cyclin D1 and Mcl-1). Cucurbitacin I also reduced the invasiveness of invasive NPC cell lines with elevated STAT3 activation. Furthermore, our data demonstrated for the first time that Cucurbitacin I harbored potent anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment-induced cell death) against human cancer. Taken together, our results suggested that Cucurbitacin I may be a potent chemopreventive agent for NPC with anti-invasion and anoikis-sensitizing activities. © The Author 2009. Published by Oxford University Press.
Persistent Identifierhttp://hdl.handle.net/10722/149727
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.439
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council, Hong Kong Government471607
The Chinese University of Hong KongCRE-2006.076
Funding Information:

Research Grant Council, Hong Kong Government (RGC Project number 471607 to V.W.Y.L.); Direct grant, The Chinese University of Hong Kong (CRE-2006.076 to V.W.Y.L.).

References

 

DC FieldValueLanguage
dc.contributor.authorLui, VWYen_US
dc.contributor.authorYau, DMen_US
dc.contributor.authorWong, EYen_US
dc.contributor.authorNg, YKen_US
dc.contributor.authorLau, CPKen_US
dc.contributor.authorHo, Yen_US
dc.contributor.authorChan, JPLen_US
dc.contributor.authorHong, Ben_US
dc.contributor.authorHo, Ken_US
dc.contributor.authorCheung, CSen_US
dc.contributor.authorTsang, CMen_US
dc.contributor.authorTsao, SWen_US
dc.contributor.authorChan, ATCen_US
dc.date.accessioned2012-06-26T05:57:42Z-
dc.date.available2012-06-26T05:57:42Z-
dc.date.issued2009en_US
dc.identifier.citationCarcinogenesis, 2009, v. 30 n. 12, p. 2085-2094en_US
dc.identifier.issn0143-3334en_US
dc.identifier.urihttp://hdl.handle.net/10722/149727-
dc.description.abstractNasopharyngeal carcinoma (NPC) is an Asian-prevalent head and neck cancer with high invasiveness. Although several important risk factors for NPC development have been identified, there is currently no preventive strategy for NPC, even in endemic regions. Signal transducer and activator of transcription 3 (STAT3) has been implicated in NPC carcinogenesis, which may serve as a potential target for cancer prevention. Here, we examined the chemopreventive potential of Cucurbitacin I, a natural-occurring selective inhibitor of JAK/STAT3, in NPC models. We hypothesized that Cucurbitacin I would prevent NPC invasion and tumor formation. Our data demonstrated that brief exposure of NPC cells to Cucurbitacin I was sufficient to significantly reduce the in vitro clonogenicity and in vivo tumorigenicity of NPC cells. The chemopreventive potential of Cucurbitacin I was further demonstrated by pre-dosing of the animals with Cucurbitacin I prior to tumor inoculation, which was found to be able to suppress tumor growth up to 7 days post-inoculation. The anti-proliferation activity of Cucurbitacin I was accompanied by downregulation of phospho-STAT3 and STAT3 target gene expression (e.g. cyclin D1 and Mcl-1). Cucurbitacin I also reduced the invasiveness of invasive NPC cell lines with elevated STAT3 activation. Furthermore, our data demonstrated for the first time that Cucurbitacin I harbored potent anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment-induced cell death) against human cancer. Taken together, our results suggested that Cucurbitacin I may be a potent chemopreventive agent for NPC with anti-invasion and anoikis-sensitizing activities. © The Author 2009. Published by Oxford University Press.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_US
dc.relation.ispartofCarcinogenesisen_US
dc.titleCucurbitacin I elicits anoikis sensitization, inhibits cellular invasion and in vivo tumor formation ability of nasopharyngeal carcinoma cellsen_US
dc.typeArticleen_US
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_US
dc.identifier.authorityTsao, SW=rp00399en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1093/carcin/bgp253en_US
dc.identifier.pmid19843642-
dc.identifier.scopuseid_2-s2.0-73949160835en_US
dc.identifier.hkuros182731-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-73949160835&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume30en_US
dc.identifier.issue12en_US
dc.identifier.spage2085en_US
dc.identifier.epage2094en_US
dc.identifier.isiWOS:000272684700016-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLui, VWY=7004231347en_US
dc.identifier.scopusauthoridYau, DM=19639624800en_US
dc.identifier.scopusauthoridWong, EY=8234468400en_US
dc.identifier.scopusauthoridNg, YK=14825706500en_US
dc.identifier.scopusauthoridLau, CPK=35737352400en_US
dc.identifier.scopusauthoridHo, Y=26654872400en_US
dc.identifier.scopusauthoridChan, JPL=35298394000en_US
dc.identifier.scopusauthoridHong, B=7202125896en_US
dc.identifier.scopusauthoridHo, K=34971221500en_US
dc.identifier.scopusauthoridCheung, CS=35080091300en_US
dc.identifier.scopusauthoridTsang, CM=24831236400en_US
dc.identifier.scopusauthoridTsao, SW=7102813116en_US
dc.identifier.scopusauthoridChan, ATC=13404833700en_US

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