Cytotoxicity of isoflavones and biflavonoids from Ormocarpum kirkii towards multi-factorial drug resistant cancer
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Fozia A Adem
- Armelle T Mbaveng
- Victor Kuete
- Matthias Heydenreich
- Albert Ndakala
- Beatrice Irungu
- Abiy Yenesew
- Thomas Efferthh
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000473047100019&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.phymed.2019.152853
- eISSN
- 1618-095X
- Externe Identifier
- Clarivate Analytics Document Solution ID: IF4JH
- PubMed Identifier: 30836216
- ISSN
- 0944-7113
- Zeitschrift
- PHYTOMEDICINE
- Schlüsselwörter
- Apoptosis
- Cancer
- Ormocarpum kirkii
- Isoflavone
- Biflavonoid
- Multi-drug resistance
- Artikelnummer
- ARTN 152853
- Datum der Veröffentlichung
- 2019
- Status
- Published
- Titel
- Cytotoxicity of isoflavones and biflavonoids from <i>Ormocarpum</i> <i>kirkii</i> towards multi-factorial drug resistant cancer
- Sub types
- Article
- Ausgabe der Zeitschrift
- 58
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Fozia A Adem
- Armelle T Mbaveng
- Victor Kuete
- Matthias Heydenreich
- Albert Ndakala
- Beatrice Irungu
- Abiy Yenesew
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2019.152853
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine
- Sprache
- en
- Artikelnummer
- 152853
- Paginierung
- 152853 - 152853
- Datum der Veröffentlichung
- 2019
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.phymed.2019.152853
- Datum der Datenerfassung
- 2023
- Titel
- Cytotoxicity of isoflavones and biflavonoids from Ormocarpum kirkii towards multi-factorial drug resistant cancer
- Ausgabe der Zeitschrift
- 58
Data source: Crossref
- Abstract
- <h4>Background</h4>While incidences of cancer are continuously increasing, drug resistance of malignant cells is observed towards almost all pharmaceuticals. Several isoflavonoids and flavonoids are known for their cytotoxicity towards various cancer cells.<h4>Purpose</h4>The aim of this study was to determine the cytotoxicity of isoflavones: osajin (1), 5,7-dihydroxy-4'-methoxy-6,8-diprenylisoflavone (2) and biflavonoids: chamaejasmin (3), 7,7″-di-O-methylchamaejasmin (4) and campylospermone A (5), a dimeric chromene [diphysin(6)] and an ester of ferullic acid with long alkyl chain [erythrinasinate (7)] isolated from the stem bark and roots of the Kenyan medicinal plant, Ormocarpum kirkii. The mode of action of compounds 2 and 4 was further investigated.<h4>Methods</h4>The cytotoxicity of compounds was determined based on the resazurin reduction assay. Caspases activation was evaluated using the caspase-Glo assay. Flow cytometry was used to analyze the cell cycle (propodium iodide (PI) staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H<sub>2</sub>DCFH-DA). CCRF-CEM leukemia cells were used as model cells for mechanistic studies.<h4>Results</h4>Compounds 1, 2 and 4 displayed IC<sub>50</sub> values below 20 µM towards CCRF-CEM and CEM/ADR5000 leukemia cells, and were further tested towards a panel of 7 carcinoma cells. The IC<sub>50</sub> values of the compounds against carcinoma cells varied from 16.90 µM (in resistant U87MG.ΔEGFR glioblastoma cells) to 48.67 µM (against HepG2 hepatocarcinoma cells) for 1, from 7.85 µM (in U87MG.ΔEGFR cells) to 14.44 µM (in resistant MDA-MB231/BCRP breast adenocarcinoma cells) for 2, from 4.96 µM (towards U87MG.ΔEGFRcells) to 7.76 µM (against MDA-MB231/BCRP cells) for 4, and from 0.07 µM (against MDA-MB231 cells) to 2.15 µM (against HepG2 cells) for doxorubicin. Compounds 2 and 4 induced apoptosis in CCRF-CEM cells mediated by MMP alteration and increased ROS production.<h4>Conclusion</h4>The present report indicates that isoflavones and biflavonoids from Ormocarpum kirkii are cytotoxic compounds with the potential of being exploited in cancer chemotherapy. Compounds 2 and 4 deserve further studies to develop new anticancer drugs to fight sensitive and resistant cancer cell lines.
- Addresses
- Department of Chemistry, University of Nairobi, P.O. Box 30197-00100, Nairobi, Kenya; Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Stawdenger Weg 5, 55128 Mainz, Germany. Electronic address: fozuti@yahoo.com.
- Autoren
- Fozia A Adem
- Armelle T Mbaveng
- Victor Kuete
- Matthias Heydenreich
- Albert Ndakala
- Beatrice Irungu
- Abiy Yenesew
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2019.152853
- eISSN
- 1618-095X
- Externe Identifier
- PubMed Identifier: 30836216
- Funding acknowledgements
- Alexander von Humboldt Foundation:
- Open access
- false
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Fabaceae
- Plant Bark
- Plant Roots
- Plants, Medicinal
- Reactive Oxygen Species
- Biflavonoids
- Isoflavones
- Caspases
- Plant Extracts
- Antineoplastic Agents, Phytogenic
- Drug Resistance, Multiple
- Cell Cycle
- Apoptosis
- Drug Resistance, Neoplasm
- Kenya
- Membrane Potential, Mitochondrial
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2019
- Paginierung
- 152853
- Datum der Veröffentlichung
- 2019
- Status
- Published
- Datum der Datenerfassung
- 2019
- Titel
- Cytotoxicity of isoflavones and biflavonoids from Ormocarpum kirkii towards multi-factorial drug resistant cancer.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 58
Data source: Europe PubMed Central
- Abstract
- BACKGROUND: While incidences of cancer are continuously increasing, drug resistance of malignant cells is observed towards almost all pharmaceuticals. Several isoflavonoids and flavonoids are known for their cytotoxicity towards various cancer cells. PURPOSE: The aim of this study was to determine the cytotoxicity of isoflavones: osajin (1), 5,7-dihydroxy-4'-methoxy-6,8-diprenylisoflavone (2) and biflavonoids: chamaejasmin (3), 7,7″-di-O-methylchamaejasmin (4) and campylospermone A (5), a dimeric chromene [diphysin(6)] and an ester of ferullic acid with long alkyl chain [erythrinasinate (7)] isolated from the stem bark and roots of the Kenyan medicinal plant, Ormocarpum kirkii. The mode of action of compounds 2 and 4 was further investigated. METHODS: The cytotoxicity of compounds was determined based on the resazurin reduction assay. Caspases activation was evaluated using the caspase-Glo assay. Flow cytometry was used to analyze the cell cycle (propodium iodide (PI) staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H2DCFH-DA). CCRF-CEM leukemia cells were used as model cells for mechanistic studies. RESULTS: Compounds 1, 2 and 4 displayed IC50 values below 20 µM towards CCRF-CEM and CEM/ADR5000 leukemia cells, and were further tested towards a panel of 7 carcinoma cells. The IC50 values of the compounds against carcinoma cells varied from 16.90 µM (in resistant U87MG.ΔEGFR glioblastoma cells) to 48.67 µM (against HepG2 hepatocarcinoma cells) for 1, from 7.85 µM (in U87MG.ΔEGFR cells) to 14.44 µM (in resistant MDA-MB231/BCRP breast adenocarcinoma cells) for 2, from 4.96 µM (towards U87MG.ΔEGFRcells) to 7.76 µM (against MDA-MB231/BCRP cells) for 4, and from 0.07 µM (against MDA-MB231 cells) to 2.15 µM (against HepG2 cells) for doxorubicin. Compounds 2 and 4 induced apoptosis in CCRF-CEM cells mediated by MMP alteration and increased ROS production. CONCLUSION: The present report indicates that isoflavones and biflavonoids from Ormocarpum kirkii are cytotoxic compounds with the potential of being exploited in cancer chemotherapy. Compounds 2 and 4 deserve further studies to develop new anticancer drugs to fight sensitive and resistant cancer cell lines.
- Date of acceptance
- 2019
- Autoren
- Fozia A Adem
- Armelle T Mbaveng
- Victor Kuete
- Matthias Heydenreich
- Albert Ndakala
- Beatrice Irungu
- Abiy Yenesew
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/30836216
- DOI
- 10.1016/j.phymed.2019.152853
- eISSN
- 1618-095X
- Zeitschrift
- Phytomedicine
- Schlüsselwörter
- Apoptosis
- Biflavonoid
- Cancer
- Isoflavone
- Multi-drug resistance
- Ormocarpum kirkii
- Antineoplastic Agents, Phytogenic
- Apoptosis
- Biflavonoids
- Caspases
- Cell Cycle
- Cell Line, Tumor
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- Fabaceae
- Humans
- Isoflavones
- Kenya
- Membrane Potential, Mitochondrial
- Plant Bark
- Plant Extracts
- Plant Roots
- Plants, Medicinal
- Reactive Oxygen Species
- Sprache
- eng
- Country
- Germany
- Paginierung
- 152853
- PII
- S0944-7113(19)30024-8
- Datum der Veröffentlichung
- 2019
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2019
- Titel
- Cytotoxicity of isoflavones and biflavonoids from Ormocarpum kirkii towards multi-factorial drug resistant cancer.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 58
Data source: PubMed
- Beziehungen:
- Property of