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Article: Recombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arrest

TitleRecombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arrest
Authors
KeywordsCombination therapy
G 2/M phase arrest
Hepatocellular carcinoma (HCC)
Ornithine transcarbamylase
Recombinant human arginase
Issue Date2009
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet
Citation
Cancer Letters, 2009, v. 277 n. 1, p. 91-100 How to Cite?
AbstractHuman hepatocellular carcinoma (HCC) has an elevated requirement for arginine in vitro, and pegylated recombinant human arginase I (rhArg-PEG), an arginine-depleting enzyme, can inhibit the growth of arginine-dependent tumors. While supplementation of the culture medium with ornithine failed to rescue Hep3B cells from growth inhibition induced by rhArg-PEG, citrulline successfully restored cell growth. The data support the roles previously proposed for ornithine transcarbamylase (OTC) in the arginine auxotrophy and rhArg-PEG sensitivity of HCC cells. Expression profiling of argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL) and OTC in 40 HCC tumor biopsy specimens predicted that 16 of the patients would be rhArg-sensitive, compared with 5 who would be sensitive to arginine deiminase (ADI), another arginine-depleting enzyme with anti-tumor activity. Furthermore, rhArg-PEG-mediated deprivation of arginine from the culture medium of different HCC cell lines produced cell cycle arrests at the G 2/M or S phase, possibly mediated by transcriptional modulation of cyclins and/or cyclin dependent kinases (CDKs). Based on these results, together with further validation of the in vivo efficacy of rhArg-PEG against HCC, we propose that the application of rhArg-PEG alone or in combination with existing chemotherapeutic drugs may represent a specific and effective therapeutic strategy against HCC. © 2008 Elsevier Ireland Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/59899
ISSN
2015 Impact Factor: 5.992
2015 SCImago Journal Rankings: 2.331
ISI Accession Number ID
Funding AgencyGrant Number
Innovation and Technology FundUIM/124
UIM/66
Funding Information:

This work was supported by Innovation and Technology Fund project no. UIM/124 and UIM/66. We state that the study sponsors had no involvement in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. We thank F.C. Tsang, C.Y. Fung, L.M. Hui, S.M. Tsui, and K.K. Cheung for assisting in the preparation of rhArg-PEG. We also thank Dr. J.S. Lee for discussion. We thank Beijing Joinn Pharmaceutical Center for their assistance in efficacy testing of rhArg-PEG in nude mice.

References

 

DC FieldValueLanguage
dc.contributor.authorLam, TLen_HK
dc.contributor.authorWong, GKYen_HK
dc.contributor.authorChong, HCen_HK
dc.contributor.authorCheng, PNMen_HK
dc.contributor.authorChoi, SCen_HK
dc.contributor.authorChow, TLen_HK
dc.contributor.authorKwok, SYen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorWheatley, DNen_HK
dc.contributor.authorLo, WHen_HK
dc.contributor.authorLeung, YCen_HK
dc.date.accessioned2010-05-31T03:59:44Z-
dc.date.available2010-05-31T03:59:44Z-
dc.date.issued2009en_HK
dc.identifier.citationCancer Letters, 2009, v. 277 n. 1, p. 91-100en_HK
dc.identifier.issn0304-3835en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59899-
dc.description.abstractHuman hepatocellular carcinoma (HCC) has an elevated requirement for arginine in vitro, and pegylated recombinant human arginase I (rhArg-PEG), an arginine-depleting enzyme, can inhibit the growth of arginine-dependent tumors. While supplementation of the culture medium with ornithine failed to rescue Hep3B cells from growth inhibition induced by rhArg-PEG, citrulline successfully restored cell growth. The data support the roles previously proposed for ornithine transcarbamylase (OTC) in the arginine auxotrophy and rhArg-PEG sensitivity of HCC cells. Expression profiling of argininosuccinate synthetase (ASS), argininosuccinate lyase (ASL) and OTC in 40 HCC tumor biopsy specimens predicted that 16 of the patients would be rhArg-sensitive, compared with 5 who would be sensitive to arginine deiminase (ADI), another arginine-depleting enzyme with anti-tumor activity. Furthermore, rhArg-PEG-mediated deprivation of arginine from the culture medium of different HCC cell lines produced cell cycle arrests at the G 2/M or S phase, possibly mediated by transcriptional modulation of cyclins and/or cyclin dependent kinases (CDKs). Based on these results, together with further validation of the in vivo efficacy of rhArg-PEG against HCC, we propose that the application of rhArg-PEG alone or in combination with existing chemotherapeutic drugs may represent a specific and effective therapeutic strategy against HCC. © 2008 Elsevier Ireland Ltd. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canleten_HK
dc.relation.ispartofCancer Lettersen_HK
dc.rightsCancer Letters. Copyright © Elsevier Ireland Ltd.en_HK
dc.subjectCombination therapyen_HK
dc.subjectG 2/M phase arresten_HK
dc.subjectHepatocellular carcinoma (HCC)en_HK
dc.subjectOrnithine transcarbamylaseen_HK
dc.subjectRecombinant human arginaseen_HK
dc.titleRecombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arresten_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0304-3835&volume=277&issue=1&spage=91&epage=100&date=2009&atitle=Recombinant+human+arginase+inhibits+proliferation+of+human+hepatocellular+carcinoma+by+inducing+cell+cycle+arresten_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.canlet.2008.11.031en_HK
dc.identifier.pmid19138817-
dc.identifier.scopuseid_2-s2.0-62249130842en_HK
dc.identifier.hkuros167038en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-62249130842&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume277en_HK
dc.identifier.issue1en_HK
dc.identifier.spage91en_HK
dc.identifier.epage100en_HK
dc.identifier.isiWOS:000265114400011-
dc.publisher.placeIrelanden_HK
dc.identifier.scopusauthoridLam, TL=8840619900en_HK
dc.identifier.scopusauthoridWong, GKY=20636425700en_HK
dc.identifier.scopusauthoridChong, HC=36804350200en_HK
dc.identifier.scopusauthoridCheng, PNM=7401618786en_HK
dc.identifier.scopusauthoridChoi, SC=37044365300en_HK
dc.identifier.scopusauthoridChow, TL=36798691900en_HK
dc.identifier.scopusauthoridKwok, SY=8601602800en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridWheatley, DN=7202668397en_HK
dc.identifier.scopusauthoridLo, WH=7201502569en_HK
dc.identifier.scopusauthoridLeung, YC=35074432700en_HK

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