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dc.contributor.authorDong, Y
dc.contributor.authorBernersPrice, SJ
dc.contributor.authorThorburn, DR
dc.contributor.authorAntalis, T
dc.contributor.authorDickinson, J
dc.contributor.authorHurst, T
dc.contributor.authorQiu, L
dc.contributor.authorKhoo, SK
dc.contributor.authorParsons, PG
dc.date.accessioned2017-09-25T00:02:44Z
dc.date.available2017-09-25T00:02:44Z
dc.date.issued1997
dc.identifier.issn0006-2952
dc.identifier.doi10.1016/S0006-2952(97)00015-4
dc.identifier.urihttp://hdl.handle.net/10072/120955
dc.description.abstractIndicators of mitochondrial function were studied in two different cell culture models of cis-diamminedichloroplatinum-II (CDDP) resistance: the intrinsically resistant human ovarian cancer cell line CI-80-13S, and resistant clones (HeLa-S1a and HeLa-S1b) generated by stable expression of the serine protease inhibitor—plasminogen activator inhibitor type-2 (PAI-2), in the human cervical cancer cell line HeLa. In both models, CDDP resistance was associated with sensitivity to killing by adriamycin, etoposide, auranofin, bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride {[Au(DPPE)2]Cl}, CdCl2 and the mitochondrial inhibitors rhodamine-123 (Rhl23), dequalinium chloride (DeCH), tetraphenylphosphonium (TPP), and ethidium bromide (EtBr) and with lower constitutive levels of ATP. Unlike the HeLa clones, CI-80-13S cells were additionally sensitive to chloramphenicol, 1-methyl-4-phenylpyridinium ion (MPP+), rotenone, thenoyltrifluoroacetone (TTFA), and antimycin A, and showed poor reduction of 1-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), suggesting a deficiency in NADH dehydrogenase and/or succinate dehydrogenase activities. Total platinum uptake and DNA-bound platinum were slightly lower in CI-80-13S than in sensitive cells. The HeLa-S1a and HeLa-S1b clones, on the other hand, showed poor reduction of triphenyltetrazolium chloride (TTC), indicative of low cytochrome c oxidase activity. Total platinum uptake by HeLa-S1a was similar to HeLa, but DNA-bound platinum was much lower than for the parent cell line. The mitochondria of CI-80-13S and HeLa-S1a showed altered morphology and were fewer in number than those of JAM and HeLa. In both models, CDDP resistance was associated with less platinum accumulation and with mitochondrial and membrane defects, brought about one case with expression of a protease inhibitor which is implicated in tumor progression. Such markers may identify tumors suitable for treatment with gold phosphine complexes or other mitochondrial inhibitors.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier Science
dc.publisher.placeUSA
dc.relation.ispartofpagefrom1673
dc.relation.ispartofpageto1682
dc.relation.ispartofjournalBiochemical Pharmacology
dc.relation.ispartofvolume53
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3214
dc.titleSerine Protease Inhibition and Mitochondrial Dysfunction Associated with Cisplatin Resistance in Human Tumour Cell Lines: Targets for Therapy
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.hasfulltextNo Full Text
gro.griffith.authorBerners-Price, Sue J.


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