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Article: Five-lipoxygenase-activating protein inhibitor MK-886 induces apoptosis in gastric cancer through upregulation of p27kip1 and bax

TitleFive-lipoxygenase-activating protein inhibitor MK-886 induces apoptosis in gastric cancer through upregulation of p27kip1 and bax
Authors
Keywords5-lipoxygenase
Apoptosis
Bax
Caspases
MK-886
Issue Date2004
PublisherWiley-Blackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JGH
Citation
Journal Of Gastroenterology And Hepatology, 2004, v. 19 n. 1, p. 31-37 How to Cite?
AbstractBackground and Aim: Products of the arachidonic acid metabolizing enzyme, 5-lipoxygenase (5-LOX), stimulate the growth of several cancer types. Inhibitors of 5-LOX and 5-LOX-activating protein (FLAP) induce apoptosis in some cancer cells. Here, the authors investigated the effect of a FLAP inhibitor, MK-886, on the inhibition of proliferation and induction of apoptosis in gastric cancer. Methods: Cell proliferation in gastric cancer cells was measured using an 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H- tetrazolium bromide assay. Apoptosis was measured using acridine orange staining and flow cytometry. Protein expression of apoptosis-related genes p53, p21waf1, p27kip1, bcl-2 families, cytochrome c, and the caspases were examined using Western blotting. Caspase-3 activity was measured using colorimetric assay of substrate cleavage. Results: MK-886 inhibited cell growth in a dose- and time-dependent manner. Apoptosis was induced in gastric cancer cells and was characterized by upregulation of p27kip1 and bax, with release of cytochrome c from mitochondria into cytosol, which initiated caspase-3 activation. Specific caspase-3 inhibitors partially blocked MK-886-induced apoptosis. Conclusion: The present results suggest that MK-886 induces apoptosis in gastric cancer cells through upregulation of p27 kip1 and bax, and that MK-886 is a potentially useful drug in gastric cancer prevention and therapy. © 2004 Blackwell Publishing Asia Pty Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/76391
ISSN
2015 Impact Factor: 3.322
2015 SCImago Journal Rankings: 1.190
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorFan, XMen_HK
dc.contributor.authorTu, SPen_HK
dc.contributor.authorLam, SKen_HK
dc.contributor.authorWang, WPen_HK
dc.contributor.authorWu, Jen_HK
dc.contributor.authorWong, WMen_HK
dc.contributor.authorYuen, MFen_HK
dc.contributor.authorLin, MCMen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorWong, BCYen_HK
dc.date.accessioned2010-09-06T07:20:44Z-
dc.date.available2010-09-06T07:20:44Z-
dc.date.issued2004en_HK
dc.identifier.citationJournal Of Gastroenterology And Hepatology, 2004, v. 19 n. 1, p. 31-37en_HK
dc.identifier.issn0815-9319en_HK
dc.identifier.urihttp://hdl.handle.net/10722/76391-
dc.description.abstractBackground and Aim: Products of the arachidonic acid metabolizing enzyme, 5-lipoxygenase (5-LOX), stimulate the growth of several cancer types. Inhibitors of 5-LOX and 5-LOX-activating protein (FLAP) induce apoptosis in some cancer cells. Here, the authors investigated the effect of a FLAP inhibitor, MK-886, on the inhibition of proliferation and induction of apoptosis in gastric cancer. Methods: Cell proliferation in gastric cancer cells was measured using an 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H- tetrazolium bromide assay. Apoptosis was measured using acridine orange staining and flow cytometry. Protein expression of apoptosis-related genes p53, p21waf1, p27kip1, bcl-2 families, cytochrome c, and the caspases were examined using Western blotting. Caspase-3 activity was measured using colorimetric assay of substrate cleavage. Results: MK-886 inhibited cell growth in a dose- and time-dependent manner. Apoptosis was induced in gastric cancer cells and was characterized by upregulation of p27kip1 and bax, with release of cytochrome c from mitochondria into cytosol, which initiated caspase-3 activation. Specific caspase-3 inhibitors partially blocked MK-886-induced apoptosis. Conclusion: The present results suggest that MK-886 induces apoptosis in gastric cancer cells through upregulation of p27 kip1 and bax, and that MK-886 is a potentially useful drug in gastric cancer prevention and therapy. © 2004 Blackwell Publishing Asia Pty Ltd.en_HK
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JGHen_HK
dc.relation.ispartofJournal of Gastroenterology and Hepatologyen_HK
dc.subject5-lipoxygenaseen_HK
dc.subjectApoptosisen_HK
dc.subjectBaxen_HK
dc.subjectCaspasesen_HK
dc.subjectMK-886en_HK
dc.subject.meshApoptosis - drug effectsen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshCaspases - metabolismen_HK
dc.subject.meshCell Cycle - drug effectsen_HK
dc.subject.meshCell Cycle Proteins - metabolismen_HK
dc.subject.meshCyclin-Dependent Kinase Inhibitor p27en_HK
dc.subject.meshCytochromes c - metabolismen_HK
dc.subject.meshFlow Cytometryen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIndoles - pharmacologyen_HK
dc.subject.meshLipoxygenase Inhibitors - pharmacologyen_HK
dc.subject.meshProto-Oncogene Proteins - metabolismen_HK
dc.subject.meshProto-Oncogene Proteins c-bcl-2en_HK
dc.subject.meshStomach Neoplasms - immunologyen_HK
dc.subject.meshTumor Cells, Cultureden_HK
dc.subject.meshTumor Suppressor Proteins - metabolismen_HK
dc.subject.meshUp-Regulationen_HK
dc.subject.meshbcl-2-Associated X Proteinen_HK
dc.titleFive-lipoxygenase-activating protein inhibitor MK-886 induces apoptosis in gastric cancer through upregulation of p27kip1 and baxen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0815-9319&volume=19&spage=31&epage=37&date=2004&atitle=Five-lipoxygenase-activating+Protein+Inhibitor+MK-886+Induces+Apoptosis+in+Gastric+Cancer+Through+Upregulation+of+p27kip1+and+baxen_HK
dc.identifier.emailYuen, MF:mfyuen@hkucc.hku.hken_HK
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_HK
dc.identifier.emailWong, BCY:bcywong@hku.hken_HK
dc.identifier.authorityYuen, MF=rp00479en_HK
dc.identifier.authorityLin, MCM=rp00746en_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1440-1746.2004.03194.xen_HK
dc.identifier.pmid14675240-
dc.identifier.scopuseid_2-s2.0-9144224191en_HK
dc.identifier.hkuros99183en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-9144224191&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume19en_HK
dc.identifier.issue1en_HK
dc.identifier.spage31en_HK
dc.identifier.epage37en_HK
dc.identifier.isiWOS:000187276300006-
dc.publisher.placeAustraliaen_HK
dc.identifier.scopusauthoridFan, XM=35187111100en_HK
dc.identifier.scopusauthoridTu, SP=7202726555en_HK
dc.identifier.scopusauthoridLam, SK=7402279473en_HK
dc.identifier.scopusauthoridWang, WP=7501765704en_HK
dc.identifier.scopusauthoridWu, J=16641439200en_HK
dc.identifier.scopusauthoridWong, WM=7403972413en_HK
dc.identifier.scopusauthoridYuen, MF=7102031955en_HK
dc.identifier.scopusauthoridLin, MCM=7404816359en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK

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