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  2. Johannes Gutenberg-Universität Mainz
  3. DFG-491381577-H
Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-9395
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dc.contributor.authorBoulos, Joelle C.-
dc.contributor.authorOmer, Ejlal A.-
dc.contributor.authorRigano, Daniela-
dc.contributor.authorFormisano, Carmen-
dc.contributor.authorChatterjee, Manik-
dc.contributor.authorLeich, Ellen-
dc.contributor.authorKlauck, Sabine M.-
dc.contributor.authorShan, Le-tian-
dc.contributor.authorEfferth, Thomas-
dc.date.accessioned2023-08-24T08:56:25Z-
dc.date.available2023-08-24T08:56:25Z-
dc.date.issued2023-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/9413-
dc.description.abstractThe majority of blood malignancies is incurable and has unforeseeable remitting-relapsing paths in response to different treatments. Cynaropicrin, a natural sesquiterpene lactone from the edible parts of the artichoke plant, has gained increased attention as a chemotherapeutic agent. In this study, we investigated the effects of cynaropicrin against multiple myeloma (MM) cells in vitro and assessed its in vivo effectiveness in a xenograft tumor zebrafish model. We showed that cynaropicrin exerted potent cytotoxicity against a panel of nine MM cell lines and two leukemia cell lines with AMO1 being the most sensitive cell line (IC50 = 1.8 ± 0.3 µM). Cynaropicrin (0.8, 1.9, 3.6 µM) dose-dependently reduced c-Myc expression and transcriptional activity in AMO1 cells that was associated with significant downregulation of STAT3, AKT, and ERK1/2. Cell cycle analysis showed that cynaropicrin treatment arrested AMO1 cells in the G2M phase along with an increase in the sub-G0G1 phase after 24 h. With prolonged treatment times, cells accumulated more in the sub-G0G1 phase, implying cell death. Using confocal microscopy, we revealed that cynaropicrin disrupted the microtubule network in U2OS cells stably expressing α-tubulin-GFP. Furthermore, we revealed that cynaropicrin promoted DNA damage in AMO1 cells leading to PAR polymer production by PARP1 hyperactivation, resulting in AIF translocation from the mitochondria to the nucleus and subsequently to a novel form of cell death, parthanatos. Finally, we demonstrated that cynaropicrin (5, 10 µM) significantly reduced tumor growth in a T-cell acute lymphoblastic leukemia (T-ALL) xenograft zebrafish model. Taken together, these results demonstrate that cynaropicrin causes potent inhibition of hematopoietic tumor cells in vitro and in vivo.en_GB
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (DFG)|491381577|Open-Access-Publikationskosten 2022–2024 Universität Mainz - Universitätsmedizin-
dc.language.isoengde
dc.rightsCC BY*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.ddc570 Biowissenschaftende_DE
dc.subject.ddc570 Life sciencesen_GB
dc.titleCynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myelomaen_GB
dc.typeZeitschriftenaufsatzde
dc.identifier.doihttp://doi.org/10.25358/openscience-9395-
jgu.type.dinitypearticleen_GB
jgu.type.versionPublished versionde
jgu.type.resourceTextde
jgu.organisation.departmentFB 09 Chemie, Pharmazie u. Geowissensch.de
jgu.organisation.number7950-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleActa pharmacologica Sinicade
jgu.journal.volumeVersion of Record (VoR)de
jgu.publisher.year2023-
jgu.publisher.nameSpringer Naturede
jgu.publisher.placeBasingstokede
jgu.publisher.issn1745-7254de
jgu.organisation.placeMainz-
jgu.subject.ddccode570de
jgu.publisher.doi10.1038/s41401-023-01117-3de
jgu.organisation.rorhttps://ror.org/023b0x485-
Appears in collections:DFG-491381577-H

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