A naturally occuring triterpene saponin ardisiacrispin B displayed cytotoxic effects in multi-factorial drug resistant cancer cells via ferroptotic and apoptotic cell death

Publication type:
Journal article
Metadata:
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

Data source: Web of Science (Lite)

Other metadata sources:
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

Data source: 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

Data source: 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

Data source: PubMed

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