Show simple item record

dc.contributor.authorLin, G
dc.contributor.authorHill, DK
dc.contributor.authorAndrejeva, G
dc.contributor.authorBoult, JKR
dc.contributor.authorTroy, H
dc.contributor.authorFong, A-CLFWT
dc.contributor.authorOrton, MR
dc.contributor.authorPanek, R
dc.contributor.authorParkes, HG
dc.contributor.authorJafar, M
dc.contributor.authorKoh, D-M
dc.contributor.authorRobinson, SP
dc.contributor.authorJudson, IR
dc.contributor.authorGriffiths, JR
dc.contributor.authorLeach, MO
dc.contributor.authorEykyn, TR
dc.contributor.authorChung, Y-L
dc.date.accessioned2020-08-13T11:48:13Z
dc.date.issued2014-07
dc.identifier.citationBritish journal of cancer, 2014, 111 (2), pp. 375 - 385
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3957
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/bjc.2014.281
dc.description.abstractBackground Dichloroacetate (DCA) has been found to have antitumour properties.Methods We investigated the cellular and metabolic responses to DCA treatment and recovery in human colorectal (HT29, HCT116 WT and HCT116 Bax-ko), prostate carcinoma cells (PC3) and HT29 xenografts by flow cytometry, western blotting, electron microscopy, (1)H and hyperpolarised (13)C-magnetic resonance spectroscopy.Results Increased expression of the autophagy markers LC3B II was observed following DCA treatment both in vitro and in vivo. We observed increased production of reactive oxygen species (ROS) and mTOR inhibition (decreased pS6 ribosomal protein and p4E-BP1 expression) as well as increased expression of MCT1 following DCA treatment. Steady-state lactate excretion and the apparent hyperpolarised [1-(13)C] pyruvate-to-lactate exchange rate (k(PL)) were decreased in DCA-treated cells, along with increased NAD(+)/NADH ratios and NAD(+). Steady-state lactate excretion and k(PL) returned to, or exceeded, control levels in cells recovered from DCA treatment, accompanied by increased NAD(+) and NADH. Reduced k(PL) with DCA treatment was found in HT29 tumour xenografts in vivo.Conclusions DCA induces autophagy in cancer cells accompanied by ROS production and mTOR inhibition, reduced lactate excretion, reduced k(PL) and increased NAD(+)/NADH ratio. The observed cellular and metabolic changes recover on cessation of treatment.
dc.formatPrint-Electronic
dc.format.extent375 - 385
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
dc.subjectCell Line, Tumor
dc.subjectHCT116 Cells
dc.subjectHT29 Cells
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Nude
dc.subjectColorectal Neoplasms
dc.subjectReactive Oxygen Species
dc.subjectLactic Acid
dc.subjectNAD
dc.subjectMicroscopy, Electron
dc.subjectRandom Allocation
dc.subjectApoptosis
dc.subjectAutophagy
dc.subjectFemale
dc.subjectTNF-Related Apoptosis-Inducing Ligand
dc.subjectTOR Serine-Threonine Kinases
dc.subjectCell Cycle Checkpoints
dc.subjectDichloroacetic Acid
dc.titleDichloroacetate induces autophagy in colorectal cancer cells and tumours.
dc.typeJournal Article
dcterms.dateAccepted2014-04-30
rioxxterms.versionofrecord10.1038/bjc.2014.281
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
rioxxterms.licenseref.startdate2014-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue2
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume111
pubs.embargo.termsNot known
icr.researchteamSarcoma Clinical Trialsen_US
icr.researchteamMagnetic Resonanceen_US
icr.researchteamPre-Clinical MRIen_US
dc.contributor.icrauthorHill, Deborahen
dc.contributor.icrauthorAndrejeva, Gabrielaen
dc.contributor.icrauthorJudson, Ianen
dc.contributor.icrauthorLeach, Martinen
dc.contributor.icrauthorRobinson, Simonen
dc.contributor.icrauthorChung, Yuen-Lien
dc.contributor.icrauthorParkes, Harolden
dc.contributor.icrauthorKoh, Dow-Muen
dc.contributor.icrauthorBoult, Jessicaen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by-nc-sa/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-sa/4.0