File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Inhibition of proteasome function induced apoptosis in gastric cancer

TitleInhibition of proteasome function induced apoptosis in gastric cancer
Authors
KeywordsApoptosis
Bar
Caspases
Gastric cancer
Ubiquitin-proteasome
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. 93 n. 4, p. 481-488 How to Cite?
AbstractThe ubiquitin-proteasome pathway plays a critical role in the degradation of cellular proteins and cell cycle control. Dysregulating the degradation of such proteins should have profound effects on tumor growth and causes cells to undergo apoptosis. The aims of this study are to evaluate the ubiquitin-proteasome pathway in gastric cancer and the potential role of pharmacological inhibition of proteasome on induction of apoptosis in gastric cancer cells. Gastric cancer cell lines AGS (p53 wild-type) and MKN-28 (p53 mutant) were treated with proteasome inhibitor MG132. The results showed that MG132 inhibited cell proliferation in AGS and MKN-28 cells in a time- and dose-dependent manner. The inhibition of cell proliferation was caused by apoptosis which was also time- and dose-dependent. AGS cells were more responsive to MG132 than MKN-28 cells. Induction of apoptosis was preceded by the activation of caspase-3, as measured by a colorimetric caspase-3 cellular activity and Western blotting of the cleavage of caspase-3 and its substrate PARP. Activation of caspase-7 was also exhibited. In addition, z-VAD-fmk, a broad spectrum caspase inhibitor, reversed apoptosis induced by MG132 in AGS and MKN28 cells. Although z-DEVD-fmk, a specific caspase-3 inhibitor, suppressed MG132-induced apoptosis in MKN28 cells, it only partially rescued the apoptotic effect in AGS cells. Caspase-3 activation was the result of release of cytochrome c from mitochondria into the cytosol, as a consequence of upregulation of bax. There were overexpressions of all the proteasome-related proteins p53, p21waf1 and p27kip1 at 4 hr after proteasome inhibition which was identified by the accumulation of ubiquitin-tagged proteins. This was accompanied by accumulation of cells at G1 phase. Our present study suggests that inhibition of proteasome function in gastric cancer cells induces apoptosis and proteasomal inhibitors have potential use as novel anticancer drugs in gastric cancer. © 2001 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/77857
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorFan, XMen_HK
dc.contributor.authorWong, BCYen_HK
dc.contributor.authorWang, WPen_HK
dc.contributor.authorZhou, XMen_HK
dc.contributor.authorCho, CHen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorLin, MCMen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorLam, SKen_HK
dc.date.accessioned2010-09-06T07:36:30Z-
dc.date.available2010-09-06T07:36:30Z-
dc.date.issued2001en_HK
dc.identifier.citationInternational Journal Of Cancer, 2001, v. 93 n. 4, p. 481-488en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77857-
dc.description.abstractThe ubiquitin-proteasome pathway plays a critical role in the degradation of cellular proteins and cell cycle control. Dysregulating the degradation of such proteins should have profound effects on tumor growth and causes cells to undergo apoptosis. The aims of this study are to evaluate the ubiquitin-proteasome pathway in gastric cancer and the potential role of pharmacological inhibition of proteasome on induction of apoptosis in gastric cancer cells. Gastric cancer cell lines AGS (p53 wild-type) and MKN-28 (p53 mutant) were treated with proteasome inhibitor MG132. The results showed that MG132 inhibited cell proliferation in AGS and MKN-28 cells in a time- and dose-dependent manner. The inhibition of cell proliferation was caused by apoptosis which was also time- and dose-dependent. AGS cells were more responsive to MG132 than MKN-28 cells. Induction of apoptosis was preceded by the activation of caspase-3, as measured by a colorimetric caspase-3 cellular activity and Western blotting of the cleavage of caspase-3 and its substrate PARP. Activation of caspase-7 was also exhibited. In addition, z-VAD-fmk, a broad spectrum caspase inhibitor, reversed apoptosis induced by MG132 in AGS and MKN28 cells. Although z-DEVD-fmk, a specific caspase-3 inhibitor, suppressed MG132-induced apoptosis in MKN28 cells, it only partially rescued the apoptotic effect in AGS cells. Caspase-3 activation was the result of release of cytochrome c from mitochondria into the cytosol, as a consequence of upregulation of bax. There were overexpressions of all the proteasome-related proteins p53, p21waf1 and p27kip1 at 4 hr after proteasome inhibition which was identified by the accumulation of ubiquitin-tagged proteins. This was accompanied by accumulation of cells at G1 phase. Our present study suggests that inhibition of proteasome function in gastric cancer cells induces apoptosis and proteasomal inhibitors have potential use as novel anticancer drugs in gastric cancer. © 2001 Wiley-Liss, Inc.en_HK
dc.languageengen_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.subjectApoptosisen_HK
dc.subjectBaren_HK
dc.subjectCaspasesen_HK
dc.subjectGastric canceren_HK
dc.subjectUbiquitin-proteasomeen_HK
dc.subject.meshAdenocarcinoma - drug therapy - enzymology - pathologyen_HK
dc.subject.meshApoptosis - drug effects - physiologyen_HK
dc.subject.meshCaspase 3en_HK
dc.subject.meshCaspase 7en_HK
dc.subject.meshCaspases - metabolismen_HK
dc.subject.meshCell Cycle - drug effectsen_HK
dc.subject.meshCell Cycle Proteins - biosynthesis - geneticsen_HK
dc.subject.meshCell Division - drug effectsen_HK
dc.subject.meshCyclin-Dependent Kinase Inhibitor p21en_HK
dc.subject.meshCyclin-Dependent Kinase Inhibitor p27en_HK
dc.subject.meshCyclins - biosynthesis - geneticsen_HK
dc.subject.meshCysteine Endopeptidases - physiologyen_HK
dc.subject.meshCysteine Proteinase Inhibitors - pharmacologyen_HK
dc.subject.meshEnzyme Activation - drug effectsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLeupeptins - pharmacologyen_HK
dc.subject.meshMultienzyme Complexes - antagonists & inhibitors - physiologyen_HK
dc.subject.meshProteasome Endopeptidase Complexen_HK
dc.subject.meshStomach Neoplasms - drug therapy - enzymology - pathologyen_HK
dc.subject.meshTumor Cells, Cultureden_HK
dc.subject.meshTumor Suppressor Protein p53 - biosynthesis - geneticsen_HK
dc.subject.meshTumor Suppressor Proteinsen_HK
dc.subject.meshUbiquitins - metabolismen_HK
dc.subject.meshUp-Regulation - drug effectsen_HK
dc.titleInhibition of proteasome function induced apoptosis in gastric canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=93&spage=481&epage=488&date=2001&atitle=Inhibition+of+proteasome+function+induced+apoptosis+in+gastric+canceren_HK
dc.identifier.emailWong, BCY:bcywong@hku.hken_HK
dc.identifier.emailLeung, SY:suetyi@hkucc.hku.hken_HK
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_HK
dc.identifier.authorityWong, BCY=rp00429en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.identifier.authorityLin, MCM=rp00746en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/ijc.1373en_HK
dc.identifier.pmid11477551-
dc.identifier.scopuseid_2-s2.0-0035882538en_HK
dc.identifier.hkuros73350en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035882538&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume93en_HK
dc.identifier.issue4en_HK
dc.identifier.spage481en_HK
dc.identifier.epage488en_HK
dc.identifier.isiWOS:000169853400004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridFan, XM=35187111100en_HK
dc.identifier.scopusauthoridWong, BCY=7402023340en_HK
dc.identifier.scopusauthoridWang, WP=7501765704en_HK
dc.identifier.scopusauthoridZhou, XM=7410092583en_HK
dc.identifier.scopusauthoridCho, CH=14067000400en_HK
dc.identifier.scopusauthoridYuen, ST=7103160927en_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK
dc.identifier.scopusauthoridLin, MCM=7404816359en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridLam, SK=7402279473en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats