dc.contributor.author
Guo, Fang
dc.contributor.author
Yang, Zhi
dc.contributor.author
Kulbe, Hagen
dc.contributor.author
Albers, Andreas E.
dc.contributor.author
Sehouli, Jalid
dc.contributor.author
Kaufmann, Andreas M.
dc.date.accessioned
2020-01-17T09:40:42Z
dc.date.available
2020-01-17T09:40:42Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/26435
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-26195
dc.description.abstract
BACKGROUND:
Disulfiram (DSF) is a drug used for treatment of alcoholism that has also displayed promising anti-cancer activity. It unfolds its effects by inhibiting the enzyme activity of aldehyde dehydrogenase (ALDH) isoforms.
METHODS:
MTT assay, spheroid formation, clonogenicity assay, qRT-PCR, and ALDH enzyme activity analysis were performed using ovarian cancer cell lines IGROV1, SKOV3 and SKOV3IP1. Cell cycle analyses and measurement of intracellular reactive oxygen species (ROS) were carried out by flow cytometry. ALDH+ and ALDH- cells were isolated by FACS sorting.
RESULTS:
ALDH activity was inhibited in ovarian cancer stem cells (the proportion of ALDH+ cells was reduced from 21.7% to 0.391%, 8.4% to 0%, 6.88% to 0.05% in cell lines IGROV1, SKOV3, and SKOV3IP1, respectively). DSF with or without the cofactor copper (Cu2+) exhibited cytotoxicity dose- and time-dependent and enhanced cisplatin-induced apoptosis. DSF + Cu2+ increased intracellular ROS levels triggering apoptosis of ovarian cancer stem cells (CSC). Significantly more colony and spheroid formation was observed in ALDH+ compared with ALDH- cells (P < 0.01). Moreover, ALDH+ cells were more resistant to cisplatin treatment compared with ALDH-cells (P < 0.05) and also exhibited a lower basal level of ROS. However, no significant difference in ROS accumulation nor in cellular viability was observed in ALDH + cells in comparison to ALDH- cells after pre-treatment with DSF (0.08 μM).
CONCLUSION:
Our findings provide evidence that DSF might be employed as a novel adjuvant chemotherapeutic agent in combination with cisplatin for treatment of ovarian cancer.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Adjuvant chemotherapy
en
dc.subject
ALDH enzyme activity
en
dc.subject
Cellular apoptosis
en
dc.subject
Cytotoxicity
en
dc.subject
Novel chemotherapeutic agent
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Inhibitory effect on ovarian cancer ALDH+ stem-like cells by Disulfiram and Copper treatment through ALDH and ROS modulation
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
109371
dcterms.bibliographicCitation.doi
10.1016/j.biopha.2019.109371
dcterms.bibliographicCitation.journaltitle
Biomedicine & Pharmacotherapy
dcterms.bibliographicCitation.originalpublishername
Elsevier
dcterms.bibliographicCitation.volume
118
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
31545281
dcterms.isPartOf.eissn
0753-3322