dc.contributor.author | Lin, G | |
dc.contributor.author | Hill, DK | |
dc.contributor.author | Andrejeva, G | |
dc.contributor.author | Boult, JKR | |
dc.contributor.author | Troy, H | |
dc.contributor.author | Fong, A-CLFWT | |
dc.contributor.author | Orton, MR | |
dc.contributor.author | Panek, R | |
dc.contributor.author | Parkes, HG | |
dc.contributor.author | Jafar, M | |
dc.contributor.author | Koh, D-M | |
dc.contributor.author | Robinson, SP | |
dc.contributor.author | Judson, IR | |
dc.contributor.author | Griffiths, JR | |
dc.contributor.author | Leach, MO | |
dc.contributor.author | Eykyn, TR | |
dc.contributor.author | Chung, Y-L | |
dc.date.accessioned | 2020-08-13T11:48:13Z | |
dc.date.issued | 2014-07-15 | |
dc.identifier.citation | British journal of cancer, 2014, 111 (2), pp. 375 - 385 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3957 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1038/bjc.2014.281 | |
dc.description.abstract | BACKGROUND: 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.format | Print-Electronic | |
dc.format.extent | 375 - 385 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-sa/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | HCT116 Cells | |
dc.subject | HT29 Cells | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Mice, Nude | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Reactive Oxygen Species | |
dc.subject | Lactic Acid | |
dc.subject | NAD | |
dc.subject | Microscopy, Electron | |
dc.subject | Random Allocation | |
dc.subject | Apoptosis | |
dc.subject | Autophagy | |
dc.subject | Female | |
dc.subject | TNF-Related Apoptosis-Inducing Ligand | |
dc.subject | TOR Serine-Threonine Kinases | |
dc.subject | Cell Cycle Checkpoints | |
dc.subject | Dichloroacetic Acid | |
dc.title | Dichloroacetate induces autophagy in colorectal cancer cells and tumours. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2014-04-30 | |
rioxxterms.versionofrecord | 10.1038/bjc.2014.281 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-sa/4.0 | |
rioxxterms.licenseref.startdate | 2014-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | British journal of cancer | |
pubs.issue | 2 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 111 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Sarcoma Clinical Trials | |
icr.researchteam | Magnetic Resonance | |
icr.researchteam | Pre-Clinical MRI | |
dc.contributor.icrauthor | Andrejeva, Gabriela | |
dc.contributor.icrauthor | Boult, Jessica | |
dc.contributor.icrauthor | Parkes, Harold | |
dc.contributor.icrauthor | Robinson, Simon | |
dc.contributor.icrauthor | Leach, Martin | |
dc.contributor.icrauthor | Chung, Yuen-Li | |