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Article: Arsenic trioxide induces apoptosis in human gastric cancer cells through up-regulation of p53 and activation of caspase-3

TitleArsenic trioxide induces apoptosis in human gastric cancer cells through up-regulation of p53 and activation of caspase-3
Authors
KeywordsApoptosis
Arsenic
Caspase
Gastric cancer
P53
Issue Date2001
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal Of Cancer, 2001, v. 91 n. 2, p. 173-179 How to Cite?
AbstractArsenic trioxide (As 2O 3) can induce clinical remission in patients suffering from acute promyelocytic leukemia, through induction of apoptosis and activation of caspases. We investigated the potential use of As 2O 3 in human gastric cancer and its possible mechanisms. Human gastric cancer cell lines AGS and MKN-28 were treated with various concentrations (0.1 to 100 μM of As 2O 3 for 24 to 72 hr. Apoptosis was determined by acridine orange staining, flow cytometry and DNA fragmentation. Protein levels of p53, p21 wafl/cipl, c-myc, bcl-2 and bax were detected by Western blotting. Effects of As 2O 3 on caspase-3 protease activity, its protein concentration and cleavage of poly(ADP)-ribose polymerase (PARP) were also studied. As 2O 3 inhibited cell growth and induced apoptosis in both cell lines, though AGS cells were more sensitive. As 2O 3 induced apoptosis in AGS cells in a concentration- and time-dependent manner. Treatment resulted in a marked increase in p53 protein levels as early as 4 hr. Co-incubation with p53 anti-sense oligo-nucleotide suppressed As 2O 3-induced intracellular p53 over-expression and apoptosis. As 2O 3 increased the activity of caspase-3, with appearance of its 17 kDa peptide fragment, and cleavage of PARP, with appearance of the 85 kDa cleavage product, both in parallel with the induction of apoptosis. Both the tripeptide caspase inhibitor zYAD-fmk and the specific caspase-3 inhibitor DEVD-fmk partially suppressed As 2O 3-induced caspase-3 activation and apoptosis. As 2O 3 inhibits cell growth and induces apoptosis in gastric cancer cells, involving p53 over-expression and activation of caspase-3. The potential use of this compound in the treatment of gastric cancer is worth further investigation. © 2001 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/48627
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
References
Errata

 

DC FieldValueLanguage
dc.contributor.authorJiang, XHen_HK
dc.contributor.authorWong, BCYen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorJiang, SHen_HK
dc.contributor.authorCho, CHen_HK
dc.contributor.authorLai, KCen_HK
dc.contributor.authorLin, MCMen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorLam, SKen_HK
dc.date.accessioned2008-05-22T04:19:26Z-
dc.date.available2008-05-22T04:19:26Z-
dc.date.issued2001en_HK
dc.identifier.citationInternational Journal Of Cancer, 2001, v. 91 n. 2, p. 173-179en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/48627-
dc.description.abstractArsenic trioxide (As 2O 3) can induce clinical remission in patients suffering from acute promyelocytic leukemia, through induction of apoptosis and activation of caspases. We investigated the potential use of As 2O 3 in human gastric cancer and its possible mechanisms. Human gastric cancer cell lines AGS and MKN-28 were treated with various concentrations (0.1 to 100 μM of As 2O 3 for 24 to 72 hr. Apoptosis was determined by acridine orange staining, flow cytometry and DNA fragmentation. Protein levels of p53, p21 wafl/cipl, c-myc, bcl-2 and bax were detected by Western blotting. Effects of As 2O 3 on caspase-3 protease activity, its protein concentration and cleavage of poly(ADP)-ribose polymerase (PARP) were also studied. As 2O 3 inhibited cell growth and induced apoptosis in both cell lines, though AGS cells were more sensitive. As 2O 3 induced apoptosis in AGS cells in a concentration- and time-dependent manner. Treatment resulted in a marked increase in p53 protein levels as early as 4 hr. Co-incubation with p53 anti-sense oligo-nucleotide suppressed As 2O 3-induced intracellular p53 over-expression and apoptosis. As 2O 3 increased the activity of caspase-3, with appearance of its 17 kDa peptide fragment, and cleavage of PARP, with appearance of the 85 kDa cleavage product, both in parallel with the induction of apoptosis. Both the tripeptide caspase inhibitor zYAD-fmk and the specific caspase-3 inhibitor DEVD-fmk partially suppressed As 2O 3-induced caspase-3 activation and apoptosis. As 2O 3 inhibits cell growth and induces apoptosis in gastric cancer cells, involving p53 over-expression and activation of caspase-3. The potential use of this compound in the treatment of gastric cancer is worth further investigation. © 2001 Wiley-Liss, Inc.en_HK
dc.format.extent349142 bytes-
dc.format.extent244752 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypeapplication/pdf-
dc.languageengen_HK
dc.languagefreen_HK
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectApoptosisen_HK
dc.subjectArsenicen_HK
dc.subjectCaspaseen_HK
dc.subjectGastric canceren_HK
dc.subjectP53en_HK
dc.subject.meshAmino Acid Chloromethyl Ketones - pharmacologyen_HK
dc.subject.meshApoptosis - drug effectsen_HK
dc.subject.meshArsenicals - pharmacologyen_HK
dc.subject.meshCaspase 3en_HK
dc.subject.meshCaspases - antagonists & inhibitors - physiologyen_HK
dc.subject.meshCell Cycle - drug effectsen_HK
dc.subject.meshCell Division - drug effectsen_HK
dc.subject.meshDNA Damageen_HK
dc.subject.meshEnzyme Activationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshOligonucleotides, Antisense - pharmacologyen_HK
dc.subject.meshOxides - pharmacologyen_HK
dc.subject.meshPoly(ADP-ribose) Polymerases - metabolismen_HK
dc.subject.meshStomach Neoplasms - drug therapy - enzymology - pathologyen_HK
dc.subject.meshTumor Cells, Cultureden_HK
dc.subject.meshTumor Suppressor Protein p53 - biosynthesisen_HK
dc.subject.meshUp-Regulationen_HK
dc.titleArsenic trioxide induces apoptosis in human gastric cancer cells through up-regulation of p53 and activation of caspase-3en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=91&issue=2&spage=173&epage=179&date=2001&atitle=Arsenic+trioxide+induces+apoptosis+in+human+gastric+cancer+cells+through+up-regulation+of+P53+and+activation+of+caspase-3en_HK
dc.identifier.emailWong, BCY:bcywong@hku.hken_HK
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.identifier.authorityLin, MCM=rp00746en_HK
dc.description.naturepostprinten_HK
dc.identifier.doi10.1002/1097-0215(200002)9999:9999<::AID-IJC1039>3.0.CO;2-Den_HK
dc.identifier.pmid11146441en_HK
dc.identifier.scopuseid_2-s2.0-0035863397en_HK
dc.identifier.hkuros58822-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035863397&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume91en_HK
dc.identifier.issue2en_HK
dc.identifier.spage173en_HK
dc.identifier.epage179en_HK
dc.identifier.isiWOS:000166159200005-
dc.publisher.placeUnited Statesen_HK
dc.relation.erratumdoi:10.1002/ijc.1442-
dc.relation.erratumeid:eid_2-s2.0-0035885225-
dc.identifier.scopusauthoridJiang, XH=36089034900en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK
dc.identifier.scopusauthoridYuen, ST=7103160927en_HK
dc.identifier.scopusauthoridJiang, SH=7404453122en_HK
dc.identifier.scopusauthoridCho, CH=14067000400en_HK
dc.identifier.scopusauthoridLai, KC=7402135595en_HK
dc.identifier.scopusauthoridLin, MCM=7404816359en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridLam, SK=7402279473en_HK

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