Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Joelle CC Boulos
- Ejlal AA Omer
- Daniela Rigano
- Carmen Formisano
- Manik Chatterjee
- Ellen Leich
- Sabine MM Klauck
- Le-tian Shan
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001019071500002&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1038/s41401-023-01117-3
- eISSN
- 1745-7254
- Externe Identifier
- Clarivate Analytics Document Solution ID: GW6A4
- PubMed Identifier: 37344563
- ISSN
- 1671-4083
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- ACTA PHARMACOLOGICA SINICA
- Schlüsselwörter
- hematological malignancies
- multiple myeloma
- cynaropicrin
- c-Myc
- microtubules
- parthanatos
- network pharmacology
- xenograft tumor zebrafish model
- Paginierung
- 2265 - 2281
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Titel
- Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma
- Sub types
- Article
- Ausgabe der Zeitschrift
- 44
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:p>The 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 (IC<jats:sub>50 </jats:sub>= 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 G<jats:sub>2</jats:sub>M phase along with an increase in the sub-G<jats:sub>0</jats:sub>G<jats:sub>1</jats:sub> phase after 24 h. With prolonged treatment times, cells accumulated more in the sub-G<jats:sub>0</jats:sub>G<jats:sub>1</jats:sub> 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.</jats:p>
- Autoren
- Joelle C Boulos
- Ejlal A Omer
- Daniela Rigano
- Carmen Formisano
- Manik Chatterjee
- Ellen Leich
- Sabine M Klauck
- Le-tian Shan
- Thomas Efferth
- DOI
- 10.1038/s41401-023-01117-3
- eISSN
- 1745-7254
- ISSN
- 1671-4083
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- Acta Pharmacologica Sinica
- Sprache
- en
- Online publication date
- 2023
- Paginierung
- 2265 - 2281
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1038/s41401-023-01117-3
- Datum der Datenerfassung
- 2023
- Titel
- Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma
- Ausgabe der Zeitschrift
- 44
Data source: Crossref
- Abstract
- The 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 (IC<sub>50 </sub>= 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 G<sub>2</sub>M phase along with an increase in the sub-G<sub>0</sub>G<sub>1</sub> phase after 24 h. With prolonged treatment times, cells accumulated more in the sub-G<sub>0</sub>G<sub>1</sub> 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.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany.
- Autoren
- Joelle C Boulos
- Ejlal A Omer
- Daniela Rigano
- Carmen Formisano
- Manik Chatterjee
- Ellen Leich
- Sabine M Klauck
- Le-Tian Shan
- Thomas Efferth
- DOI
- 10.1038/s41401-023-01117-3
- eISSN
- 1745-7254
- Externe Identifier
- PubMed Identifier: 37344563
- PubMed Central ID: PMC10618500
- Open access
- true
- ISSN
- 1671-4083
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- Acta pharmacologica Sinica
- Schlüsselwörter
- Cell Line, Tumor
- Animals
- Zebrafish
- Humans
- Multiple Myeloma
- Sesquiterpenes
- Lactones
- Tubulin
- Parthanatos
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2023
- Open access status
- Open Access
- Paginierung
- 2265 - 2281
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2023
- Titel
- Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 44
Files
https://www.nature.com/articles/s41401-023-01117-3.pdf https://europepmc.org/articles/PMC10618500?pdf=render
Data source: Europe PubMed Central
- Abstract
- The 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.
- Date of acceptance
- 2023
- Autoren
- Joelle C Boulos
- Ejlal A Omer
- Daniela Rigano
- Carmen Formisano
- Manik Chatterjee
- Ellen Leich
- Sabine M Klauck
- Le-Tian Shan
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/37344563
- DOI
- 10.1038/s41401-023-01117-3
- eISSN
- 1745-7254
- Externe Identifier
- PubMed Central ID: PMC10618500
- Ausgabe der Veröffentlichung
- 11
- Zeitschrift
- Acta Pharmacol Sin
- Schlüsselwörter
- c-Myc
- cynaropicrin
- hematological malignancies
- microtubules
- multiple myeloma
- network pharmacology
- parthanatos
- xenograft tumor zebrafish model
- Animals
- Humans
- Tubulin
- Zebrafish
- Multiple Myeloma
- Parthanatos
- Lactones
- Sesquiterpenes
- Cell Line, Tumor
- Sprache
- eng
- Country
- United States
- Paginierung
- 2265 - 2281
- PII
- 10.1038/s41401-023-01117-3
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2023
- Titel
- Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 44
Data source: PubMed
- Author's licence
- CC-BY
- Autoren
- Joelle C Boulos
- Ejlal A Omer
- Daniela Rigano
- Carmen Formisano
- Manik Chatterjee
- Ellen Leich
- Sabine M Klauck
- Le-tian Shan
- Thomas Efferth
- Hosting institution
- Universitätsbibliothek Mainz
- Sammlungen
- DFG-491381577-H
- Resource version
- Published version
- DOI
- 10.1038/s41401-023-01117-3
- Funding acknowledgements
- Deutsche Forschungsgemeinschaft (DFG)|491381577|Open-Access-Publikationskosten 2022–2024 Universität Mainz - Universitätsmedizin
- File(s) embargoed
- false
- Open access
- true
- ISSN
- 1745-7254
- Zeitschrift
- Acta pharmacologica Sinica
- Schlüsselwörter
- 570 Biowissenschaften
- 570 Life sciences
- Sprache
- eng
- Open access status
- Open Access
- Datum der Veröffentlichung
- 2023
- Public URL
- https://openscience.ub.uni-mainz.de/handle/20.500.12030/9413
- Herausgeber
- Springer Nature
- Datum der Datenerfassung
- 2023
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2023
- Zugang
- Public
- Titel
- Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma
- Ausgabe der Zeitschrift
- Version of Record (VoR)
Files
cynaropicrin_disrupts_tubulin-20230815123736975.pdf
Data source: OPENSCIENCE.UB
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