dc.contributor.author
Sumarni, Uly
dc.contributor.author
Reidel, Ulrich
dc.contributor.author
Eberle, Jürgen
dc.date.accessioned
2021-10-05T07:49:15Z
dc.date.available
2021-10-05T07:49:15Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/32190
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-31918
dc.description.abstract
New therapeutic strategies are needed for cutaneous T-cell lymphoma (CTCL), and the plant extract ingenol mebutate (PEP005) may be considered. PEP005 has been approved for actinic keratosis, and proapoptotic activities were described in different cancer cells. Here, we aimed to investigate its efficacy in four CTCL cell lines and its mode of action. While HuT-78 and HH responded with induced apoptosis as well as with loss of cell viability and cell proliferation, MyLa and SeAx remained resistant. Interestingly, both sensitive and resistant cells showed caspase-8 activation and enhanced levels of reactive oxygen species (ROS), while final caspase-3 activation was restricted to sensitive cells. Apoptosis induction was prevented by the caspase inhibitor QVD-Oph as well as by the antioxidant vitamin E. Caspase activation by PEP005 may be explained to some extent by the downregulation of the caspase antagonistic proteins c-FLIP and XIAP in sensitive cells, whereas both proteins were strongly expressed in resistant cells. Finally, PEP005 resulted in the activation of proapoptotic PKC delta, and the PKC inhibitor bisindolylmaleimide I reduced apoptosis, caspase-3 processing and ROS production, as well as restored cell viability. In conclusion, PKC delta appeared as a central player in apoptosis regulation in CTCL cells, also suggesting its therapeutic targeting.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
cutaneous T-cell lymphoma (CTCL)
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Targeting Cutaneous T-Cell Lymphoma Cells by Ingenol Mebutate (PEP005) Correlates with PKCδ Activation, ROS Induction as Well as Downregulation of XIAP and c-FLIP
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
987
dcterms.bibliographicCitation.doi
10.3390/cells10050987
dcterms.bibliographicCitation.journaltitle
Cells
dcterms.bibliographicCitation.number
5
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
33922439
dcterms.isPartOf.eissn
2073-4409