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Article: Hyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomide

TitleHyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomide
Authors
KeywordsApoptosis
Cancer resistance
Cell death
Cell structure
Cell survival
Issue Date2012
PublisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-594X
Citation
Journal of Neuro-Oncology, 2012, v. 109 n. 3, p. 467-475 How to Cite?
AbstractTemozolomide (TMZ) is standard chemotherapy for glioblastoma multiforme (GBM). Intratumoral hypoxia is common in GBM and may be associated with the development of TMZ resistance. Oxygen therapy has previously been reported to potentiate the effect of chemotherapy in cancer. In this study, we investigated whether hyperoxia can enhance the TMZ-induced cytotoxicity of human GBM cells, and whether and how it would resensitize TMZ-resistant GBM cells to TMZ. TMZ-sensitive human GBM cells (D54-S and U87-S) were treated with TMZ to develop isogenic subclones of TMZ-resistant cells (D54-R and U87-R). All cell lines were then exposed to different oxygen levels (1, 21, 40, or 80 %), with or without concomitant TMZ treatment, before assessment of cell cytotoxicity and morphology. Cell death and survival pathways elicited by TMZ and/or hyperoxia were elucidated by western blotting. Our results showed that TMZ sensitivity of both chemo-sensitive and resistant cells was enhanced significantly under hyperoxia. At the cell line-specific optimum oxygen concentration (D54-R, 80 %; U87-R, 40 %), resistant cells had the same response to TMZ as the parent chemosensitive cells under normoxia via the caspase-dependent pathway. Both TMZ and hyperoxia were associated with increased phosphorylation of ERK p44/42 MAPK (Erk1/2), but to a lesser extent in D54-R cells, suggesting that Erk1/2 activity may be involved in regulation of hyperoxia and TMZ-mediated cell death. Overall, hyperoxia enhanced TMZ toxicity in GBM cells by induction of apoptosis, possibly via MAPK-related pathways. Induced hyperoxia is a potentially promising approach for treatment of TMZ-resistant GBM.
Persistent Identifierhttp://hdl.handle.net/10722/159945
ISSN
2014 Impact Factor: 3.070
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSun, Sen_HK
dc.contributor.authorLee, Den_HK
dc.contributor.authorLee, NPen_HK
dc.contributor.authorPu, JKSen_HK
dc.contributor.authorWong, STSen_HK
dc.contributor.authorLui, WMen_HK
dc.contributor.authorFung, CFen_HK
dc.contributor.authorLeung, GKKen_HK
dc.date.accessioned2012-08-16T05:59:42Z-
dc.date.available2012-08-16T05:59:42Z-
dc.date.issued2012en_HK
dc.identifier.citationJournal of Neuro-Oncology, 2012, v. 109 n. 3, p. 467-475en_HK
dc.identifier.issn0167-594Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/159945-
dc.description.abstractTemozolomide (TMZ) is standard chemotherapy for glioblastoma multiforme (GBM). Intratumoral hypoxia is common in GBM and may be associated with the development of TMZ resistance. Oxygen therapy has previously been reported to potentiate the effect of chemotherapy in cancer. In this study, we investigated whether hyperoxia can enhance the TMZ-induced cytotoxicity of human GBM cells, and whether and how it would resensitize TMZ-resistant GBM cells to TMZ. TMZ-sensitive human GBM cells (D54-S and U87-S) were treated with TMZ to develop isogenic subclones of TMZ-resistant cells (D54-R and U87-R). All cell lines were then exposed to different oxygen levels (1, 21, 40, or 80 %), with or without concomitant TMZ treatment, before assessment of cell cytotoxicity and morphology. Cell death and survival pathways elicited by TMZ and/or hyperoxia were elucidated by western blotting. Our results showed that TMZ sensitivity of both chemo-sensitive and resistant cells was enhanced significantly under hyperoxia. At the cell line-specific optimum oxygen concentration (D54-R, 80 %; U87-R, 40 %), resistant cells had the same response to TMZ as the parent chemosensitive cells under normoxia via the caspase-dependent pathway. Both TMZ and hyperoxia were associated with increased phosphorylation of ERK p44/42 MAPK (Erk1/2), but to a lesser extent in D54-R cells, suggesting that Erk1/2 activity may be involved in regulation of hyperoxia and TMZ-mediated cell death. Overall, hyperoxia enhanced TMZ toxicity in GBM cells by induction of apoptosis, possibly via MAPK-related pathways. Induced hyperoxia is a potentially promising approach for treatment of TMZ-resistant GBM.en_HK
dc.languageengen_US
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0167-594Xen_HK
dc.relation.ispartofJournal of Neuro-Oncologyen_HK
dc.rightsThe original publication is available at www.springerlink.com-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectApoptosisen_HK
dc.subjectCancer resistanceen_HK
dc.subjectCell deathen_HK
dc.subjectCell structureen_HK
dc.subjectCell survivalen_HK
dc.titleHyperoxia resensitizes chemoresistant human glioblastoma cells to temozolomideen_HK
dc.typeArticleen_HK
dc.identifier.emailSun, S: ssun@hku.hken_HK
dc.identifier.emailLee, D: leederek@hku.hk-
dc.identifier.emailLee, NP: nikkilee@hku.hk-
dc.identifier.emailWong, STS: thiansze@graduate.hku.hk-
dc.identifier.emailLui, WM: mattlui@hku.hk-
dc.identifier.emailFung, CF: cffung@hkucc.hku.hk-
dc.identifier.emailLeung, GKK: gilberto@hku.hk-
dc.identifier.authorityLeung, GKK=rp00522en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1007/s11060-012-0923-3en_HK
dc.identifier.pmid22763762-
dc.identifier.pmcidPMC3434886-
dc.identifier.scopuseid_2-s2.0-84866053232en_HK
dc.identifier.hkuros204719en_US
dc.identifier.volume109en_US
dc.identifier.issue3-
dc.identifier.spage467en_HK
dc.identifier.epage475en_HK
dc.identifier.isiWOS:000308441700004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLeung, GKK=35965118200en_HK
dc.identifier.scopusauthoridFung, CF=52663351500en_HK
dc.identifier.scopusauthoridLui, WM=55273995200en_HK
dc.identifier.scopusauthoridWong, STS=55236638200en_HK
dc.identifier.scopusauthoridPu, JKS=35094475800en_HK
dc.identifier.scopusauthoridLee, NP=55273944900en_HK
dc.identifier.scopusauthoridLee, D=55274356000en_HK
dc.identifier.scopusauthoridSun, S=21740136100en_HK
dc.identifier.citeulike10878189-

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