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Article: The BH3-only protein, PUMA, is involved in oxaliplatin-induced apoptosis in colon cancer cells

TitleThe BH3-only protein, PUMA, is involved in oxaliplatin-induced apoptosis in colon cancer cells
Authors
KeywordsApoptosis
Colon cancer
ERK
Oxaliplatin
p53
PUMA
Issue Date2006
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm
Citation
Biochemical Pharmacology, 2006, v. 71 n. 11, p. 1540-1550 How to Cite?
AbstractOxaliplatin, the first line chemotherapeutic of colon cancer, induces damage to tumors via induction of apoptosis. PUMA (p53 up-regulate modulator of apoptosis) is an important pro-apoptotic member of Bcl-2 family and regulated mainly by p53. Here we investigated the role of PUMA in oxalipaltin-induced apoptosis and the potential mechanism. We showed that oxaliplatin-induced PUMA expression in a time- and dose-dependent manner and suppression of PUMA expression by stable transfecting anti-sense PUMA plasmid decreased oxaliplatin-induced apoptosis in colon cancer cells. By abrogating the function of p53, we further demonstrated that the induction was p53-independent. We also found that oxaliplatin could inactivate ERK and suppression of ERK activity by its specific inhibitor (PD98059), and dominant negative plasmid (DN-MEK1) enhanced the oxaliplatin-induced PUMA expression and apoptosis in a p53-independent manner. Taken together, our data suggest that PUMA plays an important role in oxaliplatin-induced apoptosis and the induction could be both p53-dependent and p53-independent. Moreover, PUMA expression and apoptosis in oxaliplatin-treated colon cancer cells could be regulated partly by ERK inactivation. Identification of the molecular components involved in regulating the cellular sensitivity to oxaliplatin may provide potential targets for development of novel compounds that may be useful in enhancement of oxaliplatin cytotoxicity in p53 deficient colon cancer. © 2006 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/70155
ISSN
2015 Impact Factor: 5.091
2015 SCImago Journal Rankings: 2.263
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWang, Xen_HK
dc.contributor.authorLi, Men_HK
dc.contributor.authorWang, Jen_HK
dc.contributor.authorYeung, CMen_HK
dc.contributor.authorZhang, Hen_HK
dc.contributor.authorKung, Hfen_HK
dc.contributor.authorJiang, Ben_HK
dc.contributor.authorChiami Lin, Men_HK
dc.date.accessioned2010-09-06T06:20:14Z-
dc.date.available2010-09-06T06:20:14Z-
dc.date.issued2006en_HK
dc.identifier.citationBiochemical Pharmacology, 2006, v. 71 n. 11, p. 1540-1550en_HK
dc.identifier.issn0006-2952en_HK
dc.identifier.urihttp://hdl.handle.net/10722/70155-
dc.description.abstractOxaliplatin, the first line chemotherapeutic of colon cancer, induces damage to tumors via induction of apoptosis. PUMA (p53 up-regulate modulator of apoptosis) is an important pro-apoptotic member of Bcl-2 family and regulated mainly by p53. Here we investigated the role of PUMA in oxalipaltin-induced apoptosis and the potential mechanism. We showed that oxaliplatin-induced PUMA expression in a time- and dose-dependent manner and suppression of PUMA expression by stable transfecting anti-sense PUMA plasmid decreased oxaliplatin-induced apoptosis in colon cancer cells. By abrogating the function of p53, we further demonstrated that the induction was p53-independent. We also found that oxaliplatin could inactivate ERK and suppression of ERK activity by its specific inhibitor (PD98059), and dominant negative plasmid (DN-MEK1) enhanced the oxaliplatin-induced PUMA expression and apoptosis in a p53-independent manner. Taken together, our data suggest that PUMA plays an important role in oxaliplatin-induced apoptosis and the induction could be both p53-dependent and p53-independent. Moreover, PUMA expression and apoptosis in oxaliplatin-treated colon cancer cells could be regulated partly by ERK inactivation. Identification of the molecular components involved in regulating the cellular sensitivity to oxaliplatin may provide potential targets for development of novel compounds that may be useful in enhancement of oxaliplatin cytotoxicity in p53 deficient colon cancer. © 2006 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharmen_HK
dc.relation.ispartofBiochemical Pharmacologyen_HK
dc.rightsBiochemical Pharmacology. Copyright © Elsevier Inc.en_HK
dc.subjectApoptosisen_HK
dc.subjectColon canceren_HK
dc.subjectERKen_HK
dc.subjectOxaliplatinen_HK
dc.subjectp53en_HK
dc.subjectPUMAen_HK
dc.titleThe BH3-only protein, PUMA, is involved in oxaliplatin-induced apoptosis in colon cancer cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-2952&volume=71&issue=11&spage=1540&epage=1550&date=2006&atitle=The+BH3-only+protein,+PUMA,+is+involved+in+oxaliplatin-induced+apoptosis+in+colon+cancer+cellsen_HK
dc.identifier.emailWang, J: jidewang@gmail.comen_HK
dc.identifier.emailChiami Lin, M: mcllin@hkucc.hku.hken_HK
dc.identifier.authorityWang, J=rp00491en_HK
dc.identifier.authorityChiami Lin, M=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bcp.2006.02.011en_HK
dc.identifier.pmid16595125-
dc.identifier.scopuseid_2-s2.0-33646480058en_HK
dc.identifier.hkuros115467en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33646480058&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume71en_HK
dc.identifier.issue11en_HK
dc.identifier.spage1540en_HK
dc.identifier.epage1550en_HK
dc.identifier.isiWOS:000237879000002-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWang, X=16044392500en_HK
dc.identifier.scopusauthoridLi, M=36067425800en_HK
dc.identifier.scopusauthoridWang, J=35309087500en_HK
dc.identifier.scopusauthoridYeung, CM=7201354151en_HK
dc.identifier.scopusauthoridZhang, H=7409198565en_HK
dc.identifier.scopusauthoridKung, Hf=7402514190en_HK
dc.identifier.scopusauthoridJiang, B=34770534200en_HK
dc.identifier.scopusauthoridChiami Lin, M=7404816359en_HK

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