dc.contributor.author
Yao, Wenhao
dc.contributor.author
Qian, Xu
dc.contributor.author
Ochsenreither, Sebastian
dc.contributor.author
Soldano, Ferrone
dc.contributor.author
DeLeo, Albert B.
dc.contributor.author
Sudhoff, Holger
dc.contributor.author
Oppel, Felix
dc.contributor.author
Kuppig, Andreas
dc.contributor.author
Klinghammer, Konrad
dc.contributor.author
Kaufmann, Andreas M.
dc.contributor.author
Albers, Andreas E.
dc.date.accessioned
2021-09-14T12:37:48Z
dc.date.available
2021-09-14T12:37:48Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/31959
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-31690
dc.description.abstract
The poor prognosis of locally advanced and metastatic head and neck squamous cell carcinoma (HNSCC) is primarily mediated by the functional properties of cancer stem cells (CSCs) and resistance to chemoradiotherapy. We investigated whether the aldehyde dehydrogenase (ALDH) inhibitor disulfiram (DSF) can enhance the sensitivity of therapy. Cell viability was assessed by the 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and apoptosis assays, and the cell cycle and reactive oxygen species (ROS) levels were evaluated by fluorescence-activated cell sorting (FACS). The radio-sensitizing effect was measured by a colony formation assay. The synergistic effects were calculated by combination index (CI) analyses. The DSF and DSF/Cu2+ inhibited the cell proliferation (inhibitory concentration 50 (IC50) of DSF and DSF/Cu2+ were 13.96 μM and 0.24 μM). DSF and cisplatin displayed a synergistic effect (CI values were <1). DSF or DSF/Cu2+ abolished the cisplatin-induced G2/M arrest (from 52.9% to 40.7% and 41.1%), and combining irradiation (IR) with DSF or DSF/Cu2+ reduced the colony formation and attenuated the G2/M arrest (from 53.6% to 40.2% and 41.9%). The combination of cisplatin, DSF or DSF/Cu2+, and IR enhanced the radio-chemo sensitivity by inducing apoptosis (42.04% and 32.21%) and ROS activity (46.3% and 37.4%). DSF and DSF/Cu2+ enhanced the sensitivity of HNSCC to cisplatin and IR. Confirming the initial data from patient-derived tumor xenograft (PDX) supported a strong rationale to repurpose DSF as a radio-chemosensitizer and to assess its therapeutic potential in a clinical setting.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
HNSCC stem cells
en
dc.subject
aldehyde dehydrogenase
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Disulfiram Acts as a Potent Radio-Chemo Sensitizer in Head and Neck Squamous Cell Carcinoma Cell Lines and Transplanted Xenografts
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
517
dcterms.bibliographicCitation.doi
10.3390/cells10030517
dcterms.bibliographicCitation.journaltitle
Cells
dcterms.bibliographicCitation.number
3
dcterms.bibliographicCitation.originalpublishername
MDPI AG
dcterms.bibliographicCitation.volume
10
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
33671083
dcterms.isPartOf.eissn
2073-4409