Cytotoxicity of epunctanone and four other phytochemicals isolated from the medicinal plants Garcinia epunctata and Ptycholobium contortum towards multi-factorial drug resistant cancer cells
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Armelle T Mbaveng
- Ghislain W Fotso
- Dominique Ngnintedo
- Victor Kuete
- Bonaventure T Ngadjui
- Felix Keumedjio
- Kerstin Andrae-Marobela
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000443714600013&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1016/j.phymed.2017.12.016
- Externe Identifier
- Clarivate Analytics Document Solution ID: GS5OG
- PubMed Identifier: 30195869
- ISSN
- 0944-7113
- Zeitschrift
- PHYTOMEDICINE
- Schlüsselwörter
- Apoptosis
- Benzophenone
- Cytotoxicity
- Multi-drug resistance
- Ferroptosis
- Phytochemicals
- Paginierung
- 112 - 119
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Titel
- Cytotoxicity of epunctanone and four other phytochemicals isolated from the medicinal plants <i>Garcinia epunctata</i> and <i>Ptycholobium contortum</i> towards multi-factorial drug resistant cancer cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 48
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Armelle T Mbaveng
- Ghislain W Fotso
- Dominique Ngnintedo
- Victor Kuete
- Bonaventure T Ngadjui
- Felix Keumedjio
- Kerstin Andrae-Marobela
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2017.12.016
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine
- Sprache
- en
- Paginierung
- 112 - 119
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.phymed.2017.12.016
- Datum der Datenerfassung
- 2023
- Titel
- Cytotoxicity of epunctanone and four other phytochemicals isolated from the medicinal plants Garcinia epunctata and Ptycholobium contortum towards multi-factorial drug resistant cancer cells
- Ausgabe der Zeitschrift
- 48
Data source: Crossref
- Abstract
- <h4>Introduction</h4>Resistance of cancer cells is a serious impediment to chemotherapy and several phytochemicals are active against multi-drug resistant (MDR) phenotypes. The cytotoxicity of five naturally occurring compounds: betulin (1), mundulea lactone (2), seputhecarpan A (3), seputheisoflavone (4) and epunctanone (5) was evaluated on a panel of 9 cancer cell lines including various sensitive and drug-resistant cell lines. The modes of action of compound 5 were further investigated.<h4>Methods</h4>The resazurin reduction assay was used to evaluate cytotoxicity of samples and ferroptotic cell death induced by compound 5; caspase-Glo assay was used to detect the activation of caspases in CCRF-CEM leukemia cells treated with compound 5. Flow cytometry was used for cell cycle analysis in CCRF-CEM cells treated with compound 5, as well as 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>Compounds 1-5 displayed cytotoxic effects in the 9 studied cancer cell lines with IC<sub>50</sub> values below 70 µM. The IC<sub>50</sub> values varied from 8.20 µM (in HCT116 (p53<sup>-/-</sup>) colon cancer cells) to 35.10 µM (against HepG2 hepatocarcinoma cells) for 1, from 8.84 µM (in CEM/ADR5000 leukemia cells) to 48.99 µM (in MDA-MB-231 breast adenocarcinoma cells) for 2, from 12.17 µM (in CEM/ADR5000 cells) to 65.08 µM (in MDA-MB-231 cells) for 3, from 23.80 µM (in U87MG.ΔEGFR glioblastoma cells) to 68.66 µM (in HCT116 (p53<sup>-/-</sup>) cells) for 4, from 4.84 µM (in HCT116 (p53<sup>-/-</sup>) cells) to 13.12 µM (in HepG2 cells) for 5 and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (in CEM/ADR5000 cells) for doxorubicin. Compound 5 induced apoptosis in CCRF-CEM cells through alteration of MMP and increase in ROS production. In addition to apoptosis, ferroptosis was also identified as another mode of cell death induced by epunctanone.<h4>Conclusions</h4>Compounds 1-5 are valuable cytotoxic compounds that could be used to combat MDR cancer cells. Benzophenoe 5 is the most active molecule and deserve more investigations to develop new anticancer drugs.
- 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, Cameroon.
- Autoren
- Armelle T Mbaveng
- Ghislain W Fotso
- Dominique Ngnintedo
- Victor Kuete
- Bonaventure T Ngadjui
- Felix Keumedjio
- Kerstin Andrae-Marobela
- Thomas Efferth
- DOI
- 10.1016/j.phymed.2017.12.016
- eISSN
- 1618-095X
- Externe Identifier
- PubMed Identifier: 30195869
- Open access
- false
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Fabaceae
- Garcinia
- Plants, Medicinal
- Reactive Oxygen Species
- Doxorubicin
- Caspases
- Plant Extracts
- Antineoplastic Agents, Phytogenic
- Drug Resistance, Multiple
- Apoptosis
- Molecular Structure
- Drug Resistance, Neoplasm
- Membrane Potential, Mitochondrial
- Hep G2 Cells
- Phytochemicals
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2017
- Paginierung
- 112 - 119
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Datum der Datenerfassung
- 2018
- Titel
- Cytotoxicity of epunctanone and four other phytochemicals isolated from the medicinal plants Garcinia epunctata and Ptycholobium contortum towards multi-factorial drug resistant cancer cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 48
Data source: Europe PubMed Central
- Abstract
- INTRODUCTION: Resistance of cancer cells is a serious impediment to chemotherapy and several phytochemicals are active against multi-drug resistant (MDR) phenotypes. The cytotoxicity of five naturally occurring compounds: betulin (1), mundulea lactone (2), seputhecarpan A (3), seputheisoflavone (4) and epunctanone (5) was evaluated on a panel of 9 cancer cell lines including various sensitive and drug-resistant cell lines. The modes of action of compound 5 were further investigated. METHODS: The resazurin reduction assay was used to evaluate cytotoxicity of samples and ferroptotic cell death induced by compound 5; caspase-Glo assay was used to detect the activation of caspases in CCRF-CEM leukemia cells treated with compound 5. Flow cytometry was used for cell cycle analysis in CCRF-CEM cells treated with compound 5, as well as detection of apoptotic cells by annexin V/PI staining, analysis of mitochondrial membrane potential (MMP) and measurement of reactive oxygen species (ROS). RESULTS: Compounds 1-5 displayed cytotoxic effects in the 9 studied cancer cell lines with IC50 values below 70 µM. The IC50 values varied from 8.20 µM (in HCT116 (p53-/-) colon cancer cells) to 35.10 µM (against HepG2 hepatocarcinoma cells) for 1, from 8.84 µM (in CEM/ADR5000 leukemia cells) to 48.99 µM (in MDA-MB-231 breast adenocarcinoma cells) for 2, from 12.17 µM (in CEM/ADR5000 cells) to 65.08 µM (in MDA-MB-231 cells) for 3, from 23.80 µM (in U87MG.ΔEGFR glioblastoma cells) to 68.66 µM (in HCT116 (p53-/-) cells) for 4, from 4.84 µM (in HCT116 (p53-/-) cells) to 13.12 µM (in HepG2 cells) for 5 and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (in CEM/ADR5000 cells) for doxorubicin. Compound 5 induced apoptosis in CCRF-CEM cells through alteration of MMP and increase in ROS production. In addition to apoptosis, ferroptosis was also identified as another mode of cell death induced by epunctanone. CONCLUSIONS: Compounds 1-5 are valuable cytotoxic compounds that could be used to combat MDR cancer cells. Benzophenoe 5 is the most active molecule and deserve more investigations to develop new anticancer drugs.
- Date of acceptance
- 2017
- Autoren
- Armelle T Mbaveng
- Ghislain W Fotso
- Dominique Ngnintedo
- Victor Kuete
- Bonaventure T Ngadjui
- Felix Keumedjio
- Kerstin Andrae-Marobela
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/30195869
- DOI
- 10.1016/j.phymed.2017.12.016
- eISSN
- 1618-095X
- Zeitschrift
- Phytomedicine
- Schlüsselwörter
- Apoptosis
- Benzophenone
- Cytotoxicity
- Ferroptosis
- Multi-drug resistance
- Phytochemicals
- Antineoplastic Agents, Phytogenic
- Apoptosis
- Caspases
- Cell Line, Tumor
- Doxorubicin
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- Fabaceae
- Garcinia
- Hep G2 Cells
- Humans
- Membrane Potential, Mitochondrial
- Molecular Structure
- Phytochemicals
- Plant Extracts
- Plants, Medicinal
- Reactive Oxygen Species
- Sprache
- eng
- Country
- Germany
- Paginierung
- 112 - 119
- PII
- S0944-7113(17)30190-3
- Datum der Veröffentlichung
- 2018
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2018
- Titel
- Cytotoxicity of epunctanone and four other phytochemicals isolated from the medicinal plants Garcinia epunctata and Ptycholobium contortum towards multi-factorial drug resistant cancer cells.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 48
Data source: PubMed
- Beziehungen:
- Property of