Cytotoxicity of ungeremine towards multi-factorial drug resistant cancer cells and induction of apoptosis, ferroptosis, necroptosis and autophagy

Publication type:
Journal article
Metadata:
Autoren
  • Armelle T Mbaveng
  • Gabin TM Bitchagno
  • Victor Kuete
  • Pierre Tane
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000485781500001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phymed.2019.152832
eISSN
1618-095X
Externe Identifier
  • Clarivate Analytics Document Solution ID: IX6GQ
  • PubMed Identifier: 31031043
ISSN
0944-7113
Zeitschrift
PHYTOMEDICINE
Schlüsselwörter
  • Alkaloid
  • Cell death
  • Multi-drug resistance
  • Natural product
Artikelnummer
ARTN 152832
Datum der Veröffentlichung
2019
Status
Published
Titel
Cytotoxicity of ungeremine towards multi-factorial drug resistant cancer cells and induction of apoptosis, ferroptosis, necroptosis and autophagy
Sub types
  • Article
Ausgabe der Zeitschrift
60

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Armelle T Mbaveng
  • Gabin TM Bitchagno
  • Victor Kuete
  • Pierre Tane
  • Thomas Efferth
DOI
10.1016/j.phymed.2019.152832
ISSN
0944-7113
Zeitschrift
Phytomedicine
Sprache
en
Artikelnummer
152832
Paginierung
152832 - 152832
Datum der Veröffentlichung
2019
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phymed.2019.152832
Datum der Datenerfassung
2023
Titel
Cytotoxicity of ungeremine towards multi-factorial drug resistant cancer cells and induction of apoptosis, ferroptosis, necroptosis and autophagy
Ausgabe der Zeitschrift
60

Data source: Crossref

Abstract
<h4>Background</h4>Successful cancer chemotherapy is hampered by resistance of cancer cells to established anticancer drugs. Numerous natural products reveal cytotoxicity towards tumor cells.<h4>Purpose</h4>The present study was aimed to determine the cytotoxicity of a betaine-type alkaloid, ungeremine, towards 9 cancer cell lines including various sensitive and drug-resistant phenotypes. The mode of action of this compound was further investigated.<h4>Methods</h4>The cytotoxicity, ferroptotic and necroptotic cell death were determined by the resazurin reduction assay. Caspase activation was evaluated using the caspase-Glo assay. Flow cytometry was applied for the analysis of cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H<sub>2</sub>DCFH-DA). Apoptotic, necroptotic and autophagic markers were determined by Western blotting. CCRF-CEM leukemia cells were used for all mechanistic studies.<h4>Results</h4>Ungeremine displayed cytotoxic activity towards the 9 cancer cell lines tested, including drug-sensitive and MDR phenotypes. The IC<sub>50</sub>values obtained varied from 3.67 µM (in MDA-MB-231-BCRP breast carcinoma cells) to 75.24 µM (against in CEM/ADR5000 leukemia cells) for ungeremine and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against CEM/ADR5000 cells) for doxorubicin (control drug). Ungeremine induced ferroptosis, necroptosis, autophagy as well as apoptosis mediated by caspase activation, MMP alteration and increase ROS production.<h4>Conclusion</h4>The present investigation showed that ungeremine is a promising cytotoxic compoundthat could be further explored in the future to develop new anticancer drugs to fight sensitive and resistant phenotypes.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany; Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
Autoren
  • Armelle T Mbaveng
  • Gabin TM Bitchagno
  • Victor Kuete
  • Pierre Tane
  • Thomas Efferth
DOI
10.1016/j.phymed.2019.152832
eISSN
1618-095X
Externe Identifier
  • PubMed Identifier: 31031043
Open access
false
ISSN
0944-7113
Zeitschrift
Phytomedicine : international journal of phytotherapy and phytopharmacology
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Reactive Oxygen Species
  • Alkaloids
  • Amaryllidaceae Alkaloids
  • Indolizines
  • Plant Extracts
  • Antineoplastic Agents, Phytogenic
  • Drug Resistance, Multiple
  • Cell Death
  • Apoptosis
  • Drug Resistance, Neoplasm
  • Autophagy
Sprache
eng
Medium
Print-Electronic
Online publication date
2019
Paginierung
152832
Datum der Veröffentlichung
2019
Status
Published
Datum der Datenerfassung
2019
Titel
Cytotoxicity of ungeremine towards multi-factorial drug resistant cancer cells and induction of apoptosis, ferroptosis, necroptosis and autophagy.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
60

Data source: Europe PubMed Central

Abstract
BACKGROUND: Successful cancer chemotherapy is hampered by resistance of cancer cells to established anticancer drugs. Numerous natural products reveal cytotoxicity towards tumor cells. PURPOSE: The present study was aimed to determine the cytotoxicity of a betaine-type alkaloid, ungeremine, towards 9 cancer cell lines including various sensitive and drug-resistant phenotypes. The mode of action of this compound was further investigated. METHODS: The cytotoxicity, ferroptotic and necroptotic cell death were determined by the resazurin reduction assay. Caspase activation was evaluated using the caspase-Glo assay. Flow cytometry was applied for the analysis of cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). Apoptotic, necroptotic and autophagic markers were determined by Western blotting. CCRF-CEM leukemia cells were used for all mechanistic studies. RESULTS: Ungeremine displayed cytotoxic activity towards the 9 cancer cell lines tested, including drug-sensitive and MDR phenotypes. The IC50values obtained varied from 3.67 µM (in MDA-MB-231-BCRP breast carcinoma cells) to 75.24 µM (against in CEM/ADR5000 leukemia cells) for ungeremine and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against CEM/ADR5000 cells) for doxorubicin (control drug). Ungeremine induced ferroptosis, necroptosis, autophagy as well as apoptosis mediated by caspase activation, MMP alteration and increase ROS production. CONCLUSION: The present investigation showed that ungeremine is a promising cytotoxic compoundthat could be further explored in the future to develop new anticancer drugs to fight sensitive and resistant phenotypes.
Date of acceptance
2019
Autoren
  • Armelle T Mbaveng
  • Gabin TM Bitchagno
  • Victor Kuete
  • Pierre Tane
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/31031043
DOI
10.1016/j.phymed.2019.152832
eISSN
1618-095X
Zeitschrift
Phytomedicine
Schlüsselwörter
  • Alkaloid
  • Cell death
  • Multi-drug resistance
  • Natural product
  • Alkaloids
  • Amaryllidaceae Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Apoptosis
  • Autophagy
  • Cell Death
  • Cell Line, Tumor
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Humans
  • Indolizines
  • Plant Extracts
  • Reactive Oxygen Species
Sprache
eng
Country
Germany
Paginierung
152832
PII
S0944-7113(19)30010-8
Datum der Veröffentlichung
2019
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2019
Titel
Cytotoxicity of ungeremine towards multi-factorial drug resistant cancer cells and induction of apoptosis, ferroptosis, necroptosis and autophagy.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
60

Data source: PubMed

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