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Article: Tumor suppressor XIAP-associated factor 1 (XAF1) cooperates with tumor necrosis factor-related apoptosis-inducing ligand to suppress colon cancer growth and trigger tumor regression

TitleTumor suppressor XIAP-associated factor 1 (XAF1) cooperates with tumor necrosis factor-related apoptosis-inducing ligand to suppress colon cancer growth and trigger tumor regression
Authors
KeywordsApoptosis
Cancer therapy
Colon cancer
Gene therapy
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
XIAP-associated factor 1 (XAF1)
Issue Date2010
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741
Citation
Cancer, 2010, v. 116 n. 5, p. 1252-1263 How to Cite?
AbstractBACKGROUND: XIAP-associated factor 1 (XAF1) antagonizes the anticaspase activity of XIAP (X-linked inhibitor of apoptosis) and functions as a tumor suppressor in colon cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known as a potential anticancer agent. In this study, the synergistic effect of XAF1 and TRAIL on colon cancer growth was investigated. METHODS: Adeno-XAF1 virus was generated and purified. Cell apoptosis was detected by flow-cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Protein expression of the different genes was determined by Western blot analysis. Tumorigenesis and tumor growth were assessed in subcutaneous nude mouse xenograft experiments. RESULTS: Stable overexpression of XAF1-sensitized colon cancer cells to TRAIL-induced apoptosis significantly increased the activity of caspase 3, 7, 8, and 9; released cytochrome c; and down-regulated XIAP, survivin, and c-IAP-2. The restoration of XAF1 expression mediated by adenovirus (adeno-XAF1) directly induced apoptosis, and synergized TRAIL-induced apoptosis in colon cancer cells. Ex vivo transduction of adeno-XAF1 suppressed colon cancer formation in vivo. Furthermore, adeno-XAF1 treatment of mice significantly inhibited tumor growth, strongly enhanced TRAIL-induced apoptosis and antitumor activity in colon cancer xenograft models in vivo, and markedly prolonged the survival. Notably, the combined treatment with adeno-XAF1 and TRAIL completely eradicated the established tumors without detectable toxicity in normal tissue. CONCLUSIONS: The combined restoration of XAF1 expression and TRAIL treatment may be a potent strategy for colon cancer therapy. © 2010 American Cancer Society.
Persistent Identifierhttp://hdl.handle.net/10722/69485
ISSN
2015 Impact Factor: 5.649
2015 SCImago Journal Rankings: 3.188
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong Kong Special Administrative RegionHKU 7482/03M
Gastroenterological Research Fund of University of Hong Kong
University Department of Medicine
National Natural Science Foundation of China30572142
30772518
Funding Information:

Supported by grants from the Research Grant Council of Hong Kong Special Administrative Region (HKU 7482/03M), the Gastroenterological Research Fund of University of Hong Kong, the University Department of Medicine research grant (to B.C.Y.W. and S.P.T.), and the National Natural Science Foundation of China (Nos. 30572142 and 30772518, to S.P.T.).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorTu, SPen_HK
dc.contributor.authorSun, YWen_HK
dc.contributor.authorCui, JTen_HK
dc.contributor.authorZou, Ben_HK
dc.contributor.authorLin, MCMen_HK
dc.contributor.authorGu, Qen_HK
dc.contributor.authorJiang, SHen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorKorneluk, RGen_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2010-09-06T06:14:06Z-
dc.date.available2010-09-06T06:14:06Z-
dc.date.issued2010en_HK
dc.identifier.citationCancer, 2010, v. 116 n. 5, p. 1252-1263en_HK
dc.identifier.issn0008-543Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/69485-
dc.description.abstractBACKGROUND: XIAP-associated factor 1 (XAF1) antagonizes the anticaspase activity of XIAP (X-linked inhibitor of apoptosis) and functions as a tumor suppressor in colon cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known as a potential anticancer agent. In this study, the synergistic effect of XAF1 and TRAIL on colon cancer growth was investigated. METHODS: Adeno-XAF1 virus was generated and purified. Cell apoptosis was detected by flow-cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Protein expression of the different genes was determined by Western blot analysis. Tumorigenesis and tumor growth were assessed in subcutaneous nude mouse xenograft experiments. RESULTS: Stable overexpression of XAF1-sensitized colon cancer cells to TRAIL-induced apoptosis significantly increased the activity of caspase 3, 7, 8, and 9; released cytochrome c; and down-regulated XIAP, survivin, and c-IAP-2. The restoration of XAF1 expression mediated by adenovirus (adeno-XAF1) directly induced apoptosis, and synergized TRAIL-induced apoptosis in colon cancer cells. Ex vivo transduction of adeno-XAF1 suppressed colon cancer formation in vivo. Furthermore, adeno-XAF1 treatment of mice significantly inhibited tumor growth, strongly enhanced TRAIL-induced apoptosis and antitumor activity in colon cancer xenograft models in vivo, and markedly prolonged the survival. Notably, the combined treatment with adeno-XAF1 and TRAIL completely eradicated the established tumors without detectable toxicity in normal tissue. CONCLUSIONS: The combined restoration of XAF1 expression and TRAIL treatment may be a potent strategy for colon cancer therapy. © 2010 American Cancer Society.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741en_HK
dc.relation.ispartofCanceren_HK
dc.rightsCancer. Copyright © John Wiley & Sons, Inc.en_HK
dc.subjectApoptosisen_HK
dc.subjectCancer therapyen_HK
dc.subjectColon canceren_HK
dc.subjectGene therapyen_HK
dc.subjectTumor necrosis factor-related apoptosis-inducing ligand (TRAIL)en_HK
dc.subjectXIAP-associated factor 1 (XAF1)en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshApoptosis - drug effectsen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshColonic Neoplasms - metabolism - prevention & control - therapyen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIntracellular Signaling Peptides and Proteinsen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred BALB Cen_HK
dc.subject.meshNeoplasm Proteins - genetics - physiology - therapeutic useen_HK
dc.subject.meshTNF-Related Apoptosis-Inducing Ligand - pharmacology - physiology - therapeutic useen_HK
dc.subject.meshTransfectionen_HK
dc.subject.meshXenograft Model Antitumor Assaysen_HK
dc.titleTumor suppressor XIAP-associated factor 1 (XAF1) cooperates with tumor necrosis factor-related apoptosis-inducing ligand to suppress colon cancer growth and trigger tumor regressionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-543X&volume=116&issue=5&spage=1252&epage=1263&date=2010&atitle=Tumor+Suppressor+XIAP-associated+Factor+1+(XAF1)+Cooperates+with+Tumor+Necrosis+Factor-related+Apoptosis-inducing+Ligand+to+Suppress+Colon+Cancer+Growth+and+Trigger+Tumor+Regressionen_HK
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_HK
dc.identifier.emailWong, BCY:bcywong@hku.hken_HK
dc.identifier.authorityLin, MCM=rp00746en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/cncr.24814en_HK
dc.identifier.pmid20082449-
dc.identifier.scopuseid_2-s2.0-77149161425en_HK
dc.identifier.hkuros168677en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77149161425&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume116en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1252en_HK
dc.identifier.epage1263en_HK
dc.identifier.isiWOS:000274772300015-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectRegulation of hTERT in relation to non-steroidal anti-inflammatory drugs in gastronintestinal carcinogenesis-
dc.identifier.scopusauthoridTu, SP=7202726555en_HK
dc.identifier.scopusauthoridSun, YW=12776261000en_HK
dc.identifier.scopusauthoridCui, JT=7401811557en_HK
dc.identifier.scopusauthoridZou, B=35228257300en_HK
dc.identifier.scopusauthoridLin, MCM=7404816359en_HK
dc.identifier.scopusauthoridGu, Q=24469982400en_HK
dc.identifier.scopusauthoridJiang, SH=7404453122en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridKorneluk, RG=7004442003en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK

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