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- Publisher Website: 10.1016/j.canlet.2008.11.031
- Scopus: eid_2-s2.0-62249130842
- PMID: 19138817
- WOS: WOS:000265114400011
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Article: Recombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arrest
Title | Recombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arrest | ||||
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Authors | |||||
Keywords | Combination therapy G 2/M phase arrest Hepatocellular carcinoma (HCC) Ornithine transcarbamylase Recombinant human arginase | ||||
Issue Date | 2009 | ||||
Publisher | Elsevier 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? | ||||
Abstract | Human 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 Identifier | http://hdl.handle.net/10722/59899 | ||||
ISSN | 2023 Impact Factor: 9.1 2023 SCImago Journal Rankings: 2.595 | ||||
ISI Accession Number ID |
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 Field | Value | Language |
---|---|---|
dc.contributor.author | Lam, TL | en_HK |
dc.contributor.author | Wong, GKY | en_HK |
dc.contributor.author | Chong, HC | en_HK |
dc.contributor.author | Cheng, PNM | en_HK |
dc.contributor.author | Choi, SC | en_HK |
dc.contributor.author | Chow, TL | en_HK |
dc.contributor.author | Kwok, SY | en_HK |
dc.contributor.author | Poon, RTP | en_HK |
dc.contributor.author | Wheatley, DN | en_HK |
dc.contributor.author | Lo, WH | en_HK |
dc.contributor.author | Leung, YC | en_HK |
dc.date.accessioned | 2010-05-31T03:59:44Z | - |
dc.date.available | 2010-05-31T03:59:44Z | - |
dc.date.issued | 2009 | en_HK |
dc.identifier.citation | Cancer Letters, 2009, v. 277 n. 1, p. 91-100 | en_HK |
dc.identifier.issn | 0304-3835 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/59899 | - |
dc.description.abstract | Human 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.language | eng | en_HK |
dc.publisher | Elsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet | en_HK |
dc.relation.ispartof | Cancer Letters | en_HK |
dc.rights | Cancer Letters. Copyright © Elsevier Ireland Ltd. | en_HK |
dc.subject | Combination therapy | en_HK |
dc.subject | G 2/M phase arrest | en_HK |
dc.subject | Hepatocellular carcinoma (HCC) | en_HK |
dc.subject | Ornithine transcarbamylase | en_HK |
dc.subject | Recombinant human arginase | en_HK |
dc.title | Recombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arrest | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://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+arrest | en_HK |
dc.identifier.email | Poon, RTP: poontp@hkucc.hku.hk | en_HK |
dc.identifier.authority | Poon, RTP=rp00446 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1016/j.canlet.2008.11.031 | en_HK |
dc.identifier.pmid | 19138817 | - |
dc.identifier.scopus | eid_2-s2.0-62249130842 | en_HK |
dc.identifier.hkuros | 167038 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-62249130842&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 277 | en_HK |
dc.identifier.issue | 1 | en_HK |
dc.identifier.spage | 91 | en_HK |
dc.identifier.epage | 100 | en_HK |
dc.identifier.isi | WOS:000265114400011 | - |
dc.publisher.place | Ireland | en_HK |
dc.identifier.scopusauthorid | Lam, TL=8840619900 | en_HK |
dc.identifier.scopusauthorid | Wong, GKY=20636425700 | en_HK |
dc.identifier.scopusauthorid | Chong, HC=36804350200 | en_HK |
dc.identifier.scopusauthorid | Cheng, PNM=7401618786 | en_HK |
dc.identifier.scopusauthorid | Choi, SC=37044365300 | en_HK |
dc.identifier.scopusauthorid | Chow, TL=36798691900 | en_HK |
dc.identifier.scopusauthorid | Kwok, SY=8601602800 | en_HK |
dc.identifier.scopusauthorid | Poon, RTP=7103097223 | en_HK |
dc.identifier.scopusauthorid | Wheatley, DN=7202668397 | en_HK |
dc.identifier.scopusauthorid | Lo, WH=7201502569 | en_HK |
dc.identifier.scopusauthorid | Leung, YC=35074432700 | en_HK |
dc.identifier.issnl | 0304-3835 | - |