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dc.contributor.authorDogra, Y
dc.contributor.authorFerguson, DC
dc.contributor.authorDodd, NJ
dc.contributor.authorSmerdon, GR
dc.contributor.authorCurnow, A
dc.contributor.authorWinyard, PG
dc.date.accessioned2016-08-17T12:35:42Z
dc.date.issued2016-07-07
dc.description.abstractMethyl-aminolevulinate-based photodynamic therapy (MAL-PDT) is utilised clinically for the treatment of non-melanoma skin cancers and pre-cancers and the hydroxypyridinone iron chelator, CP94, has successfully been demonstrated to increase MAL-PDT efficacy in an initial clinical pilot study. However, the biochemical and photochemical processes leading to CP94-enhanced photodynamic cell death, beyond the well-documented increases in accumulation of the photosensitiser protoporphyrin IX (PpIX), have not yet been fully elucidated. This investigation demonstrated that MAL-based photodynamic cell killing of cultured human squamous carcinoma cells (A431) occurred in a predominantly necrotic manner following the generation of singlet oxygen and ROS. Augmenting MAL-based photodynamic cell killing with CP94 co-treatment resulted in increased PpIX accumulation, MitoSOX-detectable ROS generation (probably of mitochondrial origin) and necrotic cell death, but did not affect singlet oxygen generation. We also report (to our knowledge, for the first time) the detection of intracellular PpIX-generated singlet oxygen in whole cells via electron paramagnetic resonance spectroscopy in conjunction with a spin trap.en_GB
dc.description.sponsorshipWe thank Professor Robert Hider, King's College London, for providing the iron chelating agent (CP94), and Drs Paul Eggleton and Jo Tarr (University of Exeter Medical School) for their assistance with the flow cytometry analysis. The Duchy Health Charity Ltd (DCH05-07), Peninsula Medical School and DDRC Healthcare (GD100015-122) are thanked for financial support. PGW and DCJF acknowledge financial support from the European Cooperation in Science and Technology, Belgium (COST Action BM1203/EU-ROS).en_GB
dc.identifier.citationVol. 9, October 2016, pp. 90 - 99en_GB
dc.identifier.doi10.1016/j.redox.2016.07.002
dc.identifier.otherS2213-2317(16)30063-5
dc.identifier.urihttp://hdl.handle.net/10871/23051
dc.language.isoenen_GB
dc.publisherElsevieren_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/27454766en_GB
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S2213231716300635en_GB
dc.rightsThis is the final version of the article. Available from Elsevier via the DOI in this record.en_GB
dc.subjectApoptosisen_GB
dc.subjectElectron paramagnetic resonance (EPR) spectrometryen_GB
dc.subjectNecrosisen_GB
dc.subjectPhotodynamic therapy (PDT)en_GB
dc.subjectProtoporphyrin IX (PpIX)en_GB
dc.subjectReactive oxygen species (ROS)en_GB
dc.subjectSkin canceren_GB
dc.titleThe hydroxypyridinone iron chelator CP94 increases methyl-aminolevulinate-based photodynamic cell killing by increasing the generation of reactive oxygen species.en_GB
dc.typeArticleen_GB
dc.date.available2016-08-17T12:35:42Z
dc.identifier.issn2213-2317
dc.descriptionPublished onlineen_GB
dc.descriptionJOURNAL ARTICLEen_GB
dc.identifier.journalRedox Biologyen_GB


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