A naturally occuring triterpene saponin ardisiacrispin B displayed cytotoxic effects in multi-factorial drug resistant cancer cells via ferroptotic and apoptotic cell death
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Armelle T Mbaveng
- Blanche L Ndontsa
- Victor Kuete
- Yves MM Nguekeu
- Ilhami Celik
- Roukayatou Mbouangouere
- Pierre Tane
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000432722700010&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.phymed.2018.03.035
- Externe Identifier
- Clarivate Analytics Document Solution ID: GG5GD
- PubMed Identifier: 29747757
- ISSN
- 0944-7113
- Zeitschrift
- PHYTOMEDICINE
- Schlüsselwörter
- Ardisiacrispin B
- Cell cycle distribution
- Cytotoxicity
- Ferroptosis
- Mitochondrial membrane potential
- Saponin
- Paginierung
- 78 - 85
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Titel
- A naturally occuring triterpene saponin ardisiacrispin B displayed cytotoxic effects in multi-factorial drug resistant cancer cells <i>via</i> ferroptotic and apoptotic cell death
- Sub types
- Article
- Ausgabe der Zeitschrift
- 43
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- Armelle T Mbaveng
- Blanche L Ndontsa
- Victor Kuete
- Yves MM Nguekeu
- İlhami Çelik
- Roukayatou Mbouangouere
- Pierre Tane
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2018.03.035
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine
- Sprache
- en
- Paginierung
- 78 - 85
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.phymed.2018.03.035
- Datum der Datenerfassung
- 2023
- Titel
- A naturally occuring triterpene saponin ardisiacrispin B displayed cytotoxic effects in multi-factorial drug resistant cancer cells via ferroptotic and apoptotic cell death
- Ausgabe der Zeitschrift
- 43
Datenquelle: Crossref
- Abstract
- <h4>Introduction</h4>Multidrug resistance of cancer cells constitutes a serious problem in chemotherapy and a challenging issue in the discovery of new cytotoxic drugs. Many saponins are known to display anti-cancer effects. In this study, the cytotoxicity and the modes of action of a naturally occuring oleanane-type tritepene saponin, ardisiacrispin B isolated from the fruit of Ardisia kivuensis Taton (Myrsinaceae) was evaluated on a panel of 9 cancer cell lines including various sensitive and drug-resistant phenotypes.<h4>Methods</h4>Resazurin reduction assay was used to evaluate cytotoxicity and ferroptotic cell death of samples; caspase-Glo assay was used to detect the activation of caspases in CCRF-CEM leukemia cells. Flow cytometry was used for cell cycle analysis and detection of apoptotic cells by annexin V/PI staining, analysis of mitochondrial membrane potential (MMP) and measurement of reactive oxygen species (ROS).<h4>Results</h4>Ardisiacrispin B displayed significant cytotoxic effects in the 9 tested cancer cell lines with IC<sub>50</sub> values below 10 µM. The IC<sub>50</sub> values ranges were 1.20 µM (towards leukemia CCRF-CEM cells) to 6.76 µM [against heptocarcinoma HepG2 cells] for ardisiacrispin B and 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against resistant CEM/ADR5000 leukemia cells) for doxorubicin. Collateral sensitivity of resistant HCT116p53<sup>-/-</sup> colon adenocarcinoma cells to ardisiacripsin B was observed. Ardisiacrispin B induced apoptosis in CCRF-CEM cells via activation of inititator caspases 8 and 9 and effector caspase 3/7, alteration of MMP and increase in ROS production. Ferroptosis also contributed to the cytotoxicity of ardisiacrispin B.<h4>Conclusions</h4>The studied oleanane-type triterpene saponin is a good cytotoxic molecule that deserve more detailed exploration in the future, to develop novel cytotoxic drugs to combat both sensitive and drug-resistant cancers.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, Mainz 55128, Germany; Department of Biochemistry, Faculty of Science, University of Dschang, Cameroon.
- Autoren
- Armelle T Mbaveng
- Blanche L Ndontsa
- Victor Kuete
- Yves MM Nguekeu
- İlhami Çelik
- Roukayatou Mbouangouere
- Pierre Tane
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2018.03.035
- eISSN
- 1618-095X
- Externe Identifier
- PubMed Identifier: 29747757
- Funding acknowledgements
- International Foundation for Science:
- Alexander von Humboldt Foundation: F5543
- IFS:
- OPCW:
- Anadolu University: 1306F110
- Open access
- false
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Schlüsselwörter
- Cell Line, Tumor
- HCT116 Cells
- Humans
- Reactive Oxygen Species
- Oleanolic Acid
- Doxorubicin
- Caspases
- Saponins
- Antineoplastic Agents, Phytogenic
- Drug Resistance, Multiple
- Apoptosis
- Drug Resistance, Neoplasm
- Membrane Potential, Mitochondrial
- Hep G2 Cells
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2018
- Paginierung
- 78 - 85
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Datum der Datenerfassung
- 2018
- Titel
- A naturally occuring triterpene saponin ardisiacrispin B displayed cytotoxic effects in multi-factorial drug resistant cancer cells via ferroptotic and apoptotic cell death.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 43
Datenquelle: Europe PubMed Central
- Abstract
- INTRODUCTION: Multidrug resistance of cancer cells constitutes a serious problem in chemotherapy and a challenging issue in the discovery of new cytotoxic drugs. Many saponins are known to display anti-cancer effects. In this study, the cytotoxicity and the modes of action of a naturally occuring oleanane-type tritepene saponin, ardisiacrispin B isolated from the fruit of Ardisia kivuensis Taton (Myrsinaceae) was evaluated on a panel of 9 cancer cell lines including various sensitive and drug-resistant phenotypes. METHODS: Resazurin reduction assay was used to evaluate cytotoxicity and ferroptotic cell death of samples; caspase-Glo assay was used to detect the activation of caspases in CCRF-CEM leukemia cells. Flow cytometry was used for cell cycle analysis and detection of apoptotic cells by annexin V/PI staining, analysis of mitochondrial membrane potential (MMP) and measurement of reactive oxygen species (ROS). RESULTS: Ardisiacrispin B displayed significant cytotoxic effects in the 9 tested cancer cell lines with IC50 values below 10 µM. The IC50 values ranges were 1.20 µM (towards leukemia CCRF-CEM cells) to 6.76 µM [against heptocarcinoma HepG2 cells] for ardisiacrispin B and 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against resistant CEM/ADR5000 leukemia cells) for doxorubicin. Collateral sensitivity of resistant HCT116p53-/- colon adenocarcinoma cells to ardisiacripsin B was observed. Ardisiacrispin B induced apoptosis in CCRF-CEM cells via activation of inititator caspases 8 and 9 and effector caspase 3/7, alteration of MMP and increase in ROS production. Ferroptosis also contributed to the cytotoxicity of ardisiacrispin B. CONCLUSIONS: The studied oleanane-type triterpene saponin is a good cytotoxic molecule that deserve more detailed exploration in the future, to develop novel cytotoxic drugs to combat both sensitive and drug-resistant cancers.
- Date of acceptance
- 2018
- Autoren
- Armelle T Mbaveng
- Blanche L Ndontsa
- Victor Kuete
- Yves MM Nguekeu
- İlhami Çelik
- Roukayatou Mbouangouere
- Pierre Tane
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/29747757
- DOI
- 10.1016/j.phymed.2018.03.035
- eISSN
- 1618-095X
- Zeitschrift
- Phytomedicine
- Schlüsselwörter
- Ardisiacrispin B
- Cell cycle distribution
- Cytotoxicity
- Ferroptosis
- Mitochondrial membrane potential
- Saponin
- Antineoplastic Agents, Phytogenic
- Apoptosis
- Caspases
- Cell Line, Tumor
- Doxorubicin
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- HCT116 Cells
- Hep G2 Cells
- Humans
- Membrane Potential, Mitochondrial
- Oleanolic Acid
- Reactive Oxygen Species
- Saponins
- Sprache
- eng
- Country
- Germany
- Paginierung
- 78 - 85
- PII
- S0944-7113(18)30070-9
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2018
- Titel
- A naturally occuring triterpene saponin ardisiacrispin B displayed cytotoxic effects in multi-factorial drug resistant cancer cells via ferroptotic and apoptotic cell death.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 43
Datenquelle: PubMed
- Beziehungen:
- Eigentum von