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Article: Mitotic arrest deficient 2 expression induces chemosensitization to a DNA-damaging agent, cisplatin, in nasopharyngeal carcinoma cells

TitleMitotic arrest deficient 2 expression induces chemosensitization to a DNA-damaging agent, cisplatin, in nasopharyngeal carcinoma cells
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2005, v. 65 n. 4, p. 1450-1458 How to Cite?
AbstractRecently, mitotic arrest deficient 2 (MAD2) - mediated spindle checkpoint is shown to induce mitotic arrest in response to DNA damage, indicating overlapping roles of the spindle checkpoint and DNA damage checkpoint. In this study, we investigated if MAD2 played a part in cellular sensitivity to DNA-damaging agents, especially cisplatin, and whether it was regulated through mitotic checkpoint. Using nine nasopharyngeal carcinoma (NPC) cell lines, we found that decreased MAD2 expression was correlated with cellular resistance to cisplatin compared with the cell lines with high levels of MAD2. Exogenous MAD2 expression in NPC cells also conferred sensitivity to DNA-damaging agents especially cisplatin but not other anticancer drugs with different mechanisms of action. The increased cisplatin sensitivity in MAD2 transfectants was associated with mitotic arrest and activation of apoptosis pathway evidenced by the increased mitotic index and apoptosis rate as well as decreased Bcl-2 and Bax ratio and expression of cleaved poly(ADP-ribose) polymerase and caspase 3. Our results indicate that the MAD2-induced chemosensitization to cisplatin in NPC cells is mediated through the induction of mitotic arrest, which in turn activates the apoptosis pathway. Our evidence further confirms the previous hypothesis that spindle checkpoint plays an important part in DNA damage-induced cell cycle arrest and suggests a novel role of MAD2 in cellular sensitivity to cisplatin.
Persistent Identifierhttp://hdl.handle.net/10722/67432
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
References

 

DC FieldValueLanguage
dc.contributor.authorHiu, WCen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorLing, MTen_HK
dc.contributor.authorYong, CWen_HK
dc.contributor.authorWang, Qen_HK
dc.contributor.authorSai, WTen_HK
dc.contributor.authorWang, Xen_HK
dc.date.accessioned2010-09-06T05:55:05Z-
dc.date.available2010-09-06T05:55:05Z-
dc.date.issued2005en_HK
dc.identifier.citationCancer Research, 2005, v. 65 n. 4, p. 1450-1458en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67432-
dc.description.abstractRecently, mitotic arrest deficient 2 (MAD2) - mediated spindle checkpoint is shown to induce mitotic arrest in response to DNA damage, indicating overlapping roles of the spindle checkpoint and DNA damage checkpoint. In this study, we investigated if MAD2 played a part in cellular sensitivity to DNA-damaging agents, especially cisplatin, and whether it was regulated through mitotic checkpoint. Using nine nasopharyngeal carcinoma (NPC) cell lines, we found that decreased MAD2 expression was correlated with cellular resistance to cisplatin compared with the cell lines with high levels of MAD2. Exogenous MAD2 expression in NPC cells also conferred sensitivity to DNA-damaging agents especially cisplatin but not other anticancer drugs with different mechanisms of action. The increased cisplatin sensitivity in MAD2 transfectants was associated with mitotic arrest and activation of apoptosis pathway evidenced by the increased mitotic index and apoptosis rate as well as decreased Bcl-2 and Bax ratio and expression of cleaved poly(ADP-ribose) polymerase and caspase 3. Our results indicate that the MAD2-induced chemosensitization to cisplatin in NPC cells is mediated through the induction of mitotic arrest, which in turn activates the apoptosis pathway. Our evidence further confirms the previous hypothesis that spindle checkpoint plays an important part in DNA damage-induced cell cycle arrest and suggests a novel role of MAD2 in cellular sensitivity to cisplatin.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshAntineoplastic Agents - pharmacologyen_HK
dc.subject.meshApoptosis - drug effects - physiologyen_HK
dc.subject.meshBenzopyrans - pharmacologyen_HK
dc.subject.meshCalcium-Binding Proteins - biosynthesis - geneticsen_HK
dc.subject.meshCaspase 3en_HK
dc.subject.meshCaspases - antagonists & inhibitors - metabolismen_HK
dc.subject.meshCell Cycle Proteinsen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshCisplatin - pharmacologyen_HK
dc.subject.meshDNA Damageen_HK
dc.subject.meshEcdysterone - analogs & derivatives - pharmacologyen_HK
dc.subject.meshEnzyme Inhibitors - pharmacologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMitosis - drug effects - physiologyen_HK
dc.subject.meshNasopharyngeal Neoplasms - drug therapy - genetics - metabolism - pathologyen_HK
dc.subject.meshNitriles - pharmacologyen_HK
dc.subject.meshProto-Oncogene Proteins c-bcl-2 - antagonists & inhibitorsen_HK
dc.subject.meshRepressor Proteinsen_HK
dc.titleMitotic arrest deficient 2 expression induces chemosensitization to a DNA-damaging agent, cisplatin, in nasopharyngeal carcinoma cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=65&issue=4&spage=1450&epage=1458&date=2005&atitle=Mitotic+arrest+deficient+2+expression+induces+chemosensitization+to+a+DNA-damaging+agent,+cisplatin,+in+nasopharyngeal+carcinoma+cellsen_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailLing, MT:patling@hkucc.hku.hken_HK
dc.identifier.emailYong, CW:ycwong@hkucc.hku.hken_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.identifier.authorityYong, CW=rp00316en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-04-0567en_HK
dc.identifier.pmid15735033-
dc.identifier.scopuseid_2-s2.0-13944278802en_HK
dc.identifier.hkuros97980en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-13944278802&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume65en_HK
dc.identifier.issue4en_HK
dc.identifier.spage1450en_HK
dc.identifier.epage1458en_HK
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHiu, WC=6506527813en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridLing, MT=7102229780en_HK
dc.identifier.scopusauthoridYong, CW=7403041798en_HK
dc.identifier.scopusauthoridWang, Q=7406910452en_HK
dc.identifier.scopusauthoridSai, WT=6507617572en_HK
dc.identifier.scopusauthoridWang, X=7501854829en_HK

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