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Article: Cucurbitacin I elicits anoikis sensitization, inhibits cellular invasion and in vivo tumor formation ability of nasopharyngeal carcinoma cells
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TitleCucurbitacin I elicits anoikis sensitization, inhibits cellular invasion and in vivo tumor formation ability of nasopharyngeal carcinoma cells
 
AuthorsLui, VWY3
Yau, DM3
Wong, EY3
Ng, YK3
Lau, CPK3
Ho, Y3
Chan, JPL3
Hong, B3
Ho, K3
Cheung, CS3
Tsang, CM1
Tsao, SW1
Chan, ATC2
 
Issue Date2009
 
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
 
CitationCarcinogenesis, 2009, v. 30 n. 12, p. 2085-2094 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgp253
 
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.
 
ISSN0143-3334
2012 Impact Factor: 5.635
2012 SCImago Journal Rankings: 2.349
 
DOIhttp://dx.doi.org/10.1093/carcin/bgp253
 
ISI Accession Number IDWOS:000272684700016
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.).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLui, VWY
 
dc.contributor.authorYau, DM
 
dc.contributor.authorWong, EY
 
dc.contributor.authorNg, YK
 
dc.contributor.authorLau, CPK
 
dc.contributor.authorHo, Y
 
dc.contributor.authorChan, JPL
 
dc.contributor.authorHong, B
 
dc.contributor.authorHo, K
 
dc.contributor.authorCheung, CS
 
dc.contributor.authorTsang, CM
 
dc.contributor.authorTsao, SW
 
dc.contributor.authorChan, ATC
 
dc.date.accessioned2012-06-26T05:57:42Z
 
dc.date.available2012-06-26T05:57:42Z
 
dc.date.issued2009
 
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.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationCarcinogenesis, 2009, v. 30 n. 12, p. 2085-2094 [How to Cite?]
DOI: http://dx.doi.org/10.1093/carcin/bgp253
 
dc.identifier.doihttp://dx.doi.org/10.1093/carcin/bgp253
 
dc.identifier.epage2094
 
dc.identifier.hkuros182731
 
dc.identifier.isiWOS:000272684700016
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.).

 
dc.identifier.issn0143-3334
2012 Impact Factor: 5.635
2012 SCImago Journal Rankings: 2.349
 
dc.identifier.issue12
 
dc.identifier.pmid19843642
 
dc.identifier.scopuseid_2-s2.0-73949160835
 
dc.identifier.spage2085
 
dc.identifier.urihttp://hdl.handle.net/10722/149727
 
dc.identifier.volume30
 
dc.languageeng
 
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofCarcinogenesis
 
dc.relation.referencesReferences in Scopus
 
dc.titleCucurbitacin I elicits anoikis sensitization, inhibits cellular invasion and in vivo tumor formation ability of nasopharyngeal carcinoma cells
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Prince of Wales Hospital Hong Kong
  3. Chinese University of Hong Kong