Cytotoxicity of the crude extract and constituents of the bark of Fagara tessmannii towards multi-factorial drug resistant cancer cells

Publication type:
Journal article
Metadata:
Autoren
  • Armelle T Mbaveng
  • Francois Damen
  • Ilhami Celik
  • Pierre Tane
  • Victor Kuete
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000463126800004&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.jep.2019.01.031
Externe Identifier
  • Clarivate Analytics Document Solution ID: HR4OW
  • PubMed Identifier: 30703492
ISSN
0378-8741
Zeitschrift
JOURNAL OF ETHNOPHARMACOLOGY
Schlüsselwörter
  • Alkaloids
  • Apoptosis
  • Cytotoxicity
  • Fagara tessmanniii
  • Multi-drug resistance
  • Traditional medicine
Paginierung
28 - 37
Datum der Veröffentlichung
2019
Status
Published
Titel
Cytotoxicity of the crude extract and constituents of the bark of <i>Fagara tessmannii</i> towards multi-factorial drug resistant cancer cells
Sub types
  • Article
Ausgabe der Zeitschrift
235

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Armelle T Mbaveng
  • Francois Damen
  • İlhami Çelik
  • Pierre Tane
  • Victor Kuete
  • Thomas Efferth
DOI
10.1016/j.jep.2019.01.031
ISSN
0378-8741
Zeitschrift
Journal of Ethnopharmacology
Sprache
en
Paginierung
28 - 37
Datum der Veröffentlichung
2019
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.jep.2019.01.031
Datum der Datenerfassung
2023
Titel
Cytotoxicity of the crude extract and constituents of the bark of Fagara tessmannii towards multi-factorial drug resistant cancer cells
Ausgabe der Zeitschrift
235

Data source: Crossref

Abstract
<h4>Ethnopharmacological relevance</h4>Fagara tessmannii Engl. is an African medicinal plant used in Cameroonian traditional medicine to treat various types of cancers.<h4>Aim of the study</h4>This work was designed to determine the cytotoxicity of the crude extract (FTB), fractions (FTBa-d) and compounds isolated from the bark of Fagara tessmannii, namely lupeol (1), fagaramide (2), zanthoxyline (3), hesperidin (4), nitidine chloride (5), fagaridine chloride (6), and β-sitosterol-3-O-β-<sub>D</sub>-glucopyranoside (7). The study was extended to the mode of induction of apoptosis by FTB, compounds 5 and 6.<h4>Materials and methods</h4>The resazurin reduction assay was used to evaluate the cytotoxicity of samples. The cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were measured by flow cytometry. Column chromatography was used for the purification of FTB. Meanwhile, nuclear magnetic resonance (NMR) spectroscopic analysis was applied for structural elucidation.<h4>Results</h4>The crude extract, fractions FTBa, FTBc, FTBd as well as compounds 5 and 6 revealed cytotoxicity towards the 9 tested cancer cell lines. The IC<sub>50</sub> values ranged from 17.34 µg/mL (towards U87MG.ΔEGFR glioblastoma cells) to 40.68 µg/mL (against CCRF-CEM leukemia cells) for FTB, from 16.78 µg/mL (towards U87. MGΔEGFR cells) to 37.42 µg/mL (against CEM/ADR5000 leukemia cells) for FTBa, from 19.47 µg/mL (towards U87. MG glioblastoma cells) to 41.62 µg/mL (against CCRF-CEM cells) for FTBc, from 14.17 µg/mL (against HCT116p53<sup>-/-</sup> colon adenocarcinoma cells) to 22.28 µg/mL (towards CEM-ADR5000 cells) for FTBd, from 1.75 µM (against CCRF-CEM cells) to 23.52 µM (against U87. MGΔEGFR cells) for compound 5, from 1.69 µM (against CCRF-CEM cells) to 22.06 µM (against HepG2 hepatocarcinoma cells) for compound 6 and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against CEM/ADR5000 cells) for doxorubicin. FTB induced apoptosis in CCRF-CEM cells mediated by enhanced ROS production. Compound 5 induced apoptosis through caspases activation and increase ROS production. Meanwhile, 6 induced apoptosis mediated by caspases activation, MMP alteration and enhanced ROS production.<h4>Conclusion</h4>Fagara tessmannii as well as its constituents 5 and 6 revealed considerable cytotoxicity and may be suitable candidates deserving to be further explored to develop new anticancer drugs to combat 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
  • Francois Damen
  • İlhami Çelik
  • Pierre Tane
  • Victor Kuete
  • Thomas Efferth
DOI
10.1016/j.jep.2019.01.031
eISSN
1872-7573
Externe Identifier
  • PubMed Identifier: 30703492
Funding acknowledgements
  • Anadolu University: 1306F110
Open access
false
ISSN
0378-8741
Zeitschrift
Journal of ethnopharmacology
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Zanthoxylum
  • Plant Bark
  • Neoplasms
  • Reactive Oxygen Species
  • Doxorubicin
  • Plant Extracts
  • Antineoplastic Agents, Phytogenic
  • Inhibitory Concentration 50
  • Cell Cycle
  • Apoptosis
  • Drug Resistance, Neoplasm
  • Membrane Potential, Mitochondrial
Sprache
eng
Medium
Print-Electronic
Online publication date
2019
Paginierung
28 - 37
Datum der Veröffentlichung
2019
Status
Published
Datum der Datenerfassung
2019
Titel
Cytotoxicity of the crude extract and constituents of the bark of Fagara tessmannii towards multi-factorial drug resistant cancer cells.
Sub types
  • Comparative Study
  • Journal Article
Ausgabe der Zeitschrift
235

Data source: Europe PubMed Central

Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Fagara tessmannii Engl. is an African medicinal plant used in Cameroonian traditional medicine to treat various types of cancers. AIM OF THE STUDY: This work was designed to determine the cytotoxicity of the crude extract (FTB), fractions (FTBa-d) and compounds isolated from the bark of Fagara tessmannii, namely lupeol (1), fagaramide (2), zanthoxyline (3), hesperidin (4), nitidine chloride (5), fagaridine chloride (6), and β-sitosterol-3-O-β-D-glucopyranoside (7). The study was extended to the mode of induction of apoptosis by FTB, compounds 5 and 6. MATERIALS AND METHODS: The resazurin reduction assay was used to evaluate the cytotoxicity of samples. The cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were measured by flow cytometry. Column chromatography was used for the purification of FTB. Meanwhile, nuclear magnetic resonance (NMR) spectroscopic analysis was applied for structural elucidation. RESULTS: The crude extract, fractions FTBa, FTBc, FTBd as well as compounds 5 and 6 revealed cytotoxicity towards the 9 tested cancer cell lines. The IC50 values ranged from 17.34 µg/mL (towards U87MG.ΔEGFR glioblastoma cells) to 40.68 µg/mL (against CCRF-CEM leukemia cells) for FTB, from 16.78 µg/mL (towards U87. MGΔEGFR cells) to 37.42 µg/mL (against CEM/ADR5000 leukemia cells) for FTBa, from 19.47 µg/mL (towards U87. MG glioblastoma cells) to 41.62 µg/mL (against CCRF-CEM cells) for FTBc, from 14.17 µg/mL (against HCT116p53-/- colon adenocarcinoma cells) to 22.28 µg/mL (towards CEM-ADR5000 cells) for FTBd, from 1.75 µM (against CCRF-CEM cells) to 23.52 µM (against U87. MGΔEGFR cells) for compound 5, from 1.69 µM (against CCRF-CEM cells) to 22.06 µM (against HepG2 hepatocarcinoma cells) for compound 6 and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against CEM/ADR5000 cells) for doxorubicin. FTB induced apoptosis in CCRF-CEM cells mediated by enhanced ROS production. Compound 5 induced apoptosis through caspases activation and increase ROS production. Meanwhile, 6 induced apoptosis mediated by caspases activation, MMP alteration and enhanced ROS production. CONCLUSION: Fagara tessmannii as well as its constituents 5 and 6 revealed considerable cytotoxicity and may be suitable candidates deserving to be further explored to develop new anticancer drugs to combat sensitive and resistant phenotypes.
Date of acceptance
2019
Autoren
  • Armelle T Mbaveng
  • Francois Damen
  • İlhami Çelik
  • Pierre Tane
  • Victor Kuete
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/30703492
DOI
10.1016/j.jep.2019.01.031
eISSN
1872-7573
Zeitschrift
J Ethnopharmacol
Schlüsselwörter
  • 2´,7´-dichlorodihydrofluorescein diacetate
  • 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide
  • Alkaloids
  • Apoptosis
  • Cytotoxicity
  • Fagara tessmanniii
  • Multi-drug resistance
  • Traditional medicine
  • dimethyl sulfoxide
  • doxorubicin
  • fagaramide
  • fagaridine chloride
  • hesperidin
  • hydrogen peroxide
  • lupeol
  • nitidine chloride
  • valinomycin
  • zanthoxyline
  • β-sitosterol-3-O-β-(D)-glucopyranoside
  • Antineoplastic Agents, Phytogenic
  • Apoptosis
  • Cell Cycle
  • Cell Line, Tumor
  • Doxorubicin
  • Drug Resistance, Neoplasm
  • Humans
  • Inhibitory Concentration 50
  • Membrane Potential, Mitochondrial
  • Neoplasms
  • Plant Bark
  • Plant Extracts
  • Reactive Oxygen Species
  • Zanthoxylum
Sprache
eng
Country
Ireland
Paginierung
28 - 37
PII
S0378-8741(18)34252-1
Datum der Veröffentlichung
2019
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2019
Titel
Cytotoxicity of the crude extract and constituents of the bark of Fagara tessmannii towards multi-factorial drug resistant cancer cells.
Sub types
  • Comparative Study
  • Journal Article
Ausgabe der Zeitschrift
235

Data source: PubMed

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