Cytotoxicity of a naturally occurring furoquinoline alkaloid and four acridone alkaloids towards multi-factorial drug-resistant cancer cells
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Victor Kuete
- Hugues Fouotsa
- Armelle T Mbaveng
- Benjamin Wiench
- Augustin E Nkengfack
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000360551300009&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.phymed.2015.07.002
- eISSN
- 1618-095X
- Externe Identifier
- Clarivate Analytics Document Solution ID: CQ4CH
- PubMed Identifier: 26321744
- ISSN
- 0944-7113
- Ausgabe der Veröffentlichung
- 10
- Zeitschrift
- PHYTOMEDICINE
- Schlüsselwörter
- 1,3-Dimethoxy-10-methylacridone
- Ac ridone
- Apoptosis
- Cytotoxicity
- Furoquinoline
- Multi drug resistance
- Paginierung
- 946 - 951
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Titel
- Cytotoxicity of a naturally occurring furoquinoline alkaloid and four acridone alkaloids towards multi-factorial drug-resistant cancer cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 22
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Victor Kuete
- Hugues Fouotsa
- Armelle T Mbaveng
- Benjamin Wiench
- Augustin E Nkengfack
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2015.07.002
- ISSN
- 0944-7113
- Ausgabe der Veröffentlichung
- 10
- Zeitschrift
- Phytomedicine
- Sprache
- en
- Paginierung
- 946 - 951
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.phymed.2015.07.002
- Datum der Datenerfassung
- 2023
- Titel
- Cytotoxicity of a naturally occurring furoquinoline alkaloid and four acridone alkaloids towards multi-factorial drug-resistant cancer cells
- Ausgabe der Zeitschrift
- 22
Data source: Crossref
- Abstract
- <h4>Introduction</h4>Chemotherapy is one of the preferred mode of treatment of malignancies, but is complicated by the expression of diverse resistance mechanisms of cancer cells.<h4>Methods</h4>In the present study, we investigated the cytotoxicity of five alkaloids including a furoquinoline montrofoline (1) and four acridones namely 1-hydroxy-4-methoxy-10-methylacridone (2), norevoxanthine (3), evoxanthine (4), 1,3-dimethoxy-10-methylacridone (5) against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analyzed via flow cytometry.<h4>Results</h4>Furoquinoline 1 as well as the acridone alkaloids 2-5 displayed cytotoxic effects with IC50 values below 138 µM on all the 9 tested cancer cell lines. The IC50 values ranged from 41.56 µM (towards hepatocarinoma HepG2 cells) to 90.66 µM [towards colon carcinoma HCT116 (p53(-/-)) cells] for 1, from 6.78 µM [towards HCT116 (p53(-/-)) cells) to 106.47 µM [towards breast adenocarcinoma MDA-MB-231-pcDNA cells] for 2, from 5.72 µM (towards gliobastoma U87MG.ΔEGFR cells) to 137.62 µM (towards leukemia CCRF-CEM cells] for 3, from 6.11 µM [towards HCT116 (p53(+/+)) cells] to 80.99 µM (towards HepG2 cells] for 4, from 3.38 µM (towards MDA-MB-231-BCRP cells) to 58.10 µM (towards leukemia CEM/ADR5000 cells] for 5 and from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (against CEM/ADR5000 cells) for doxorubicin. Acridone alkaloid 5 induced apoptosis in CCRF-CEM leukemia cells, mediated by increased ROS production.<h4>Conclusions</h4>The five tested alkaloids and mostly acridone 5 are potential cytotoxic natural products that deserve more investigations to develop novel cytotoxic compounds against multifactorial drug-resistant cancers.
- 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, Dschang,Cameroon.
- Autoren
- Victor Kuete
- Hugues Fouotsa
- Armelle T Mbaveng
- Benjamin Wiench
- Augustin E Nkengfack
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2015.07.002
- eISSN
- 1618-095X
- Externe Identifier
- PubMed Identifier: 26321744
- Open access
- false
- ISSN
- 0944-7113
- Ausgabe der Veröffentlichung
- 10
- Zeitschrift
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Reactive Oxygen Species
- Alkaloids
- Caspases
- Antineoplastic Agents, Phytogenic
- Inhibitory Concentration 50
- Drug Resistance, Multiple
- Cell Cycle
- Apoptosis
- Molecular Structure
- Drug Resistance, Neoplasm
- Membrane Potential, Mitochondrial
- Acridones
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2015
- Paginierung
- 946 - 951
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum der Datenerfassung
- 2015
- Titel
- Cytotoxicity of a naturally occurring furoquinoline alkaloid and four acridone alkaloids towards multi-factorial drug-resistant cancer cells.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 22
Data source: Europe PubMed Central
- Abstract
- INTRODUCTION: Chemotherapy is one of the preferred mode of treatment of malignancies, but is complicated by the expression of diverse resistance mechanisms of cancer cells. METHODS: In the present study, we investigated the cytotoxicity of five alkaloids including a furoquinoline montrofoline (1) and four acridones namely 1-hydroxy-4-methoxy-10-methylacridone (2), norevoxanthine (3), evoxanthine (4), 1,3-dimethoxy-10-methylacridone (5) against 9 drug-sensitive and multidrug-resistant (MDR) cancer cell lines. The resazurin reduction assay was used to evaluate the cytotoxicity of these compounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle, mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were all analyzed via flow cytometry. RESULTS: Furoquinoline 1 as well as the acridone alkaloids 2-5 displayed cytotoxic effects with IC50 values below 138 µM on all the 9 tested cancer cell lines. The IC50 values ranged from 41.56 µM (towards hepatocarinoma HepG2 cells) to 90.66 µM [towards colon carcinoma HCT116 (p53(-/-)) cells] for 1, from 6.78 µM [towards HCT116 (p53(-/-)) cells) to 106.47 µM [towards breast adenocarcinoma MDA-MB-231-pcDNA cells] for 2, from 5.72 µM (towards gliobastoma U87MG.ΔEGFR cells) to 137.62 µM (towards leukemia CCRF-CEM cells] for 3, from 6.11 µM [towards HCT116 (p53(+/+)) cells] to 80.99 µM (towards HepG2 cells] for 4, from 3.38 µM (towards MDA-MB-231-BCRP cells) to 58.10 µM (towards leukemia CEM/ADR5000 cells] for 5 and from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (against CEM/ADR5000 cells) for doxorubicin. Acridone alkaloid 5 induced apoptosis in CCRF-CEM leukemia cells, mediated by increased ROS production. CONCLUSIONS: The five tested alkaloids and mostly acridone 5 are potential cytotoxic natural products that deserve more investigations to develop novel cytotoxic compounds against multifactorial drug-resistant cancers.
- Date of acceptance
- 2015
- Autoren
- Victor Kuete
- Hugues Fouotsa
- Armelle T Mbaveng
- Benjamin Wiench
- Augustin E Nkengfack
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/26321744
- DOI
- 10.1016/j.phymed.2015.07.002
- eISSN
- 1618-095X
- Ausgabe der Veröffentlichung
- 10
- Zeitschrift
- Phytomedicine
- Schlüsselwörter
- 1,3-Dimethoxy-10-methylacridone
- Acridone
- Apoptosis
- Cytotoxicity
- Furoquinoline
- Multi-drug resistance
- Acridones
- Alkaloids
- Antineoplastic Agents, Phytogenic
- Apoptosis
- Caspases
- Cell Cycle
- Cell Line, Tumor
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- Humans
- Inhibitory Concentration 50
- Membrane Potential, Mitochondrial
- Molecular Structure
- Reactive Oxygen Species
- Sprache
- eng
- Country
- Germany
- Paginierung
- 946 - 951
- PII
- S0944-7113(15)00216-0
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2015
- Titel
- Cytotoxicity of a naturally occurring furoquinoline alkaloid and four acridone alkaloids towards multi-factorial drug-resistant cancer cells.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 22
Data source: PubMed
- Beziehungen:
- Property of