Cytotoxicity of the methanol extracts and compounds of Brucea antidysenterica (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines

Publication type:
Journal article
Metadata:
Autoren
  • Laetitia M Youmbi
  • Yves SD Makong
  • Armelle T Mbaveng
  • Simplice B Tankeo
  • Ghislain W Fotso
  • Bruno L Ndjakou
  • Jean D Wansi
  • Veronique P Beng
  • Norbert Sewald
  • Bonaventure T Ngadjui
  • Thomas Efferth
  • Victor Kuete
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000935205000002&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1186/s12906-023-03877-1
eISSN
2662-7671
Externe Identifier
  • Clarivate Analytics Document Solution ID: 9C1SH
  • PubMed Identifier: 36793009
Ausgabe der Veröffentlichung
1
Zeitschrift
BMC COMPLEMENTARY MEDICINE AND THERAPIES
Schlüsselwörter
  • Apoptosis
  • Brucea antidysenterica
  • Cytotoxicity
  • Multidrug resistance
  • Hydnocarpin
  • Simaroubaceae
Artikelnummer
ARTN 48
Datum der Veröffentlichung
2023
Status
Published
Titel
Cytotoxicity of the methanol extracts and compounds of <i>Brucea antidysenterica</i> (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines
Sub types
  • Article
Ausgabe der Zeitschrift
23

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Cancer remains a global health concern and constitutes an important barrier to increasing life expectancy. Malignant cells rapidly develop drug resistance leading to many clinical therapeutic failures. The importance of medicinal plants as an alternative to classical drug discovery to fight cancer is well known. <jats:italic>Brucea antidysenterica</jats:italic> is an African medicinal plant traditionally used to treat cancer, dysentery, malaria, diarrhea, stomach aches, helminthic infections, fever, and asthma. The present work was designed to identify the cytotoxic constituents of <jats:italic>Brucea antidysenterica</jats:italic> on a broad range of cancer cell lines and to demonstrate the mode of induction of apoptosis of the most active samples.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Seven phytochemicals were isolated from the leaves (BAL) and stem (BAS) extract of <jats:italic>Brucea antidysenterica</jats:italic> by column chromatography and structurally elucidated using spectroscopic techniques. The antiproliferative effects of the crude extracts and compounds against 9 human cancer cell lines were evaluated by the resazurin reduction assay (RRA). The activity in cell lines was assessed by the Caspase-Glo assay. The cell cycle distribution, apoptosis via propidium iodide (PI) staining, mitochondrial membrane potential (MMP) through 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and the reactive oxygen species (ROS) via 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining, were investigated by flow cytometry.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Phytochemical studies of the botanicals (BAL and BAS) led to the isolation of seven compounds. BAL and its constituents 3, (3-(3-Methyl-1-oxo-2-butenyl))1<jats:italic>H</jats:italic> indole (<jats:bold>1</jats:bold>) and hydnocarpin (<jats:bold>2</jats:bold>), as well as the reference compound, doxorubicin, had antiproliferative activity against 9 cancer cell lines. The IC<jats:sub>50</jats:sub> values varied from 17.42 µg/mL (against CCRF-CEM leukemia cells) to 38.70 µg/mL (against HCT116 <jats:italic>p53</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> colon adenocarcinoma cells) for BAL, from 19.11 µM (against CCRF-CEM cells) to 47.50 µM (against MDA-MB-231-<jats:italic>BCRP</jats:italic> adenocarcinoma cells) for compound <jats:bold>1</jats:bold>, and from 4.07 µM (against MDA-MB-231-<jats:italic>pcDNA</jats:italic> cells) to 11.44 µM (against HCT116 <jats:italic>p53</jats:italic><jats:sup>+<jats:italic>/</jats:italic>+</jats:sup> cells) for compound <jats:bold>2</jats:bold>. Interestingly, hypersensitivity of resistant cancer cells to compound <jats:bold>2</jats:bold> was also observed. BAL and hydnocarpin induced apoptosis in CCRF-CEM cells mediated by caspase activation, the alteration of MMP, and increased ROS levels.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>BAL and its constituents, mostly compound <jats:bold>2</jats:bold>, are potential antiproliferative products from <jats:italic>Brucea antidysenterica</jats:italic>. Other studies will be necessary in the perspective of the discovery of new antiproliferative agents to fight against resistance to anticancer drugs. </jats:p> </jats:sec>
Autoren
  • Laetitia M Youmbi
  • Yves SD Makong
  • Armelle T Mbaveng
  • Simplice B Tankeo
  • Ghislain W Fotso
  • Bruno L Ndjakou
  • Jean D Wansi
  • Veronique P Beng
  • Norbert Sewald
  • Bonaventure T Ngadjui
  • Thomas Efferth
  • Victor Kuete
DOI
10.1186/s12906-023-03877-1
eISSN
2662-7671
Ausgabe der Veröffentlichung
1
Zeitschrift
BMC Complementary Medicine and Therapies
Sprache
en
Artikelnummer
48
Online publication date
2023
Status
Published online
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1186/s12906-023-03877-1
Datum der Datenerfassung
2023
Titel
Cytotoxicity of the methanol extracts and compounds of Brucea antidysenterica (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines
Ausgabe der Zeitschrift
23

Data source: Crossref

Abstract
<h4>Background</h4>Cancer remains a global health concern and constitutes an important barrier to increasing life expectancy. Malignant cells rapidly develop drug resistance leading to many clinical therapeutic failures. The importance of medicinal plants as an alternative to classical drug discovery to fight cancer is well known. Brucea antidysenterica is an African medicinal plant traditionally used to treat cancer, dysentery, malaria, diarrhea, stomach aches, helminthic infections, fever, and asthma. The present work was designed to identify the cytotoxic constituents of Brucea antidysenterica on a broad range of cancer cell lines and to demonstrate the mode of induction of apoptosis of the most active samples.<h4>Methods</h4>Seven phytochemicals were isolated from the leaves (BAL) and stem (BAS) extract of Brucea antidysenterica by column chromatography and structurally elucidated using spectroscopic techniques. The antiproliferative effects of the crude extracts and compounds against 9 human cancer cell lines were evaluated by the resazurin reduction assay (RRA). The activity in cell lines was assessed by the Caspase-Glo assay. The cell cycle distribution, apoptosis via propidium iodide (PI) staining, mitochondrial membrane potential (MMP) through 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and the reactive oxygen species (ROS) via 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining, were investigated by flow cytometry.<h4>Results</h4>Phytochemical studies of the botanicals (BAL and BAS) led to the isolation of seven compounds. BAL and its constituents 3, (3-(3-Methyl-1-oxo-2-butenyl))1H indole (1) and hydnocarpin (2), as well as the reference compound, doxorubicin, had antiproliferative activity against 9 cancer cell lines. The IC<sub>50</sub> values varied from 17.42 µg/mL (against CCRF-CEM leukemia cells) to 38.70 µg/mL (against HCT116 p53<sup>-/-</sup> colon adenocarcinoma cells) for BAL, from 19.11 µM (against CCRF-CEM cells) to 47.50 µM (against MDA-MB-231-BCRP adenocarcinoma cells) for compound 1, and from 4.07 µM (against MDA-MB-231-pcDNA cells) to 11.44 µM (against HCT116 p53<sup>+/+</sup> cells) for compound 2. Interestingly, hypersensitivity of resistant cancer cells to compound 2 was also observed. BAL and hydnocarpin induced apoptosis in CCRF-CEM cells mediated by caspase activation, the alteration of MMP, and increased ROS levels.<h4>Conclusion</h4>BAL and its constituents, mostly compound 2, are potential antiproliferative products from Brucea antidysenterica. Other studies will be necessary in the perspective of the discovery of new antiproliferative agents to fight against resistance to anticancer drugs.
Addresses
  • Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
Autoren
  • Laetitia M Youmbi
  • Yves SD Makong
  • Armelle T Mbaveng
  • Simplice B Tankeo
  • Ghislain W Fotso
  • Bruno L Ndjakou
  • Jean D Wansi
  • Veronique P Beng
  • Norbert Sewald
  • Bonaventure T Ngadjui
  • Thomas Efferth
  • Victor Kuete
DOI
10.1186/s12906-023-03877-1
eISSN
2662-7671
Externe Identifier
  • PubMed Identifier: 36793009
  • PubMed Central ID: PMC9930359
Open access
true
ISSN
2662-7671
Ausgabe der Veröffentlichung
1
Zeitschrift
BMC complementary medicine and therapies
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Simaroubaceae
  • Brucea
  • Adenocarcinoma
  • Colonic Neoplasms
  • Reactive Oxygen Species
  • Methanol
  • Caspases
  • Neoplasm Proteins
  • Plant Extracts
  • Antineoplastic Agents, Phytogenic
  • Drug Resistance, Neoplasm
  • Tumor Suppressor Protein p53
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
Sprache
eng
Medium
Electronic
Online publication date
2023
Open access status
Open Access
Paginierung
48
Datum der Veröffentlichung
2023
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2023
Titel
Cytotoxicity of the methanol extracts and compounds of Brucea antidysenterica (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
23

Files

https://bmccomplementmedtherapies.biomedcentral.com/counter/pdf/10.1186/s12906-023-03877-1 https://europepmc.org/articles/PMC9930359?pdf=render

Data source: Europe PubMed Central

Abstract
BACKGROUND: Cancer remains a global health concern and constitutes an important barrier to increasing life expectancy. Malignant cells rapidly develop drug resistance leading to many clinical therapeutic failures. The importance of medicinal plants as an alternative to classical drug discovery to fight cancer is well known. Brucea antidysenterica is an African medicinal plant traditionally used to treat cancer, dysentery, malaria, diarrhea, stomach aches, helminthic infections, fever, and asthma. The present work was designed to identify the cytotoxic constituents of Brucea antidysenterica on a broad range of cancer cell lines and to demonstrate the mode of induction of apoptosis of the most active samples. METHODS: Seven phytochemicals were isolated from the leaves (BAL) and stem (BAS) extract of Brucea antidysenterica by column chromatography and structurally elucidated using spectroscopic techniques. The antiproliferative effects of the crude extracts and compounds against 9 human cancer cell lines were evaluated by the resazurin reduction assay (RRA). The activity in cell lines was assessed by the Caspase-Glo assay. The cell cycle distribution, apoptosis via propidium iodide (PI) staining, mitochondrial membrane potential (MMP) through 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and the reactive oxygen species (ROS) via 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining, were investigated by flow cytometry. RESULTS: Phytochemical studies of the botanicals (BAL and BAS) led to the isolation of seven compounds. BAL and its constituents 3, (3-(3-Methyl-1-oxo-2-butenyl))1H indole (1) and hydnocarpin (2), as well as the reference compound, doxorubicin, had antiproliferative activity against 9 cancer cell lines. The IC50 values varied from 17.42 µg/mL (against CCRF-CEM leukemia cells) to 38.70 µg/mL (against HCT116 p53-/- colon adenocarcinoma cells) for BAL, from 19.11 µM (against CCRF-CEM cells) to 47.50 µM (against MDA-MB-231-BCRP adenocarcinoma cells) for compound 1, and from 4.07 µM (against MDA-MB-231-pcDNA cells) to 11.44 µM (against HCT116 p53+/+ cells) for compound 2. Interestingly, hypersensitivity of resistant cancer cells to compound 2 was also observed. BAL and hydnocarpin induced apoptosis in CCRF-CEM cells mediated by caspase activation, the alteration of MMP, and increased ROS levels. CONCLUSION: BAL and its constituents, mostly compound 2, are potential antiproliferative products from Brucea antidysenterica. Other studies will be necessary in the perspective of the discovery of new antiproliferative agents to fight against resistance to anticancer drugs.
Date of acceptance
2023
Autoren
  • Laetitia M Youmbi
  • Yves SD Makong
  • Armelle T Mbaveng
  • Simplice B Tankeo
  • Ghislain W Fotso
  • Bruno L Ndjakou
  • Jean D Wansi
  • Veronique P Beng
  • Norbert Sewald
  • Bonaventure T Ngadjui
  • Thomas Efferth
  • Victor Kuete
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/36793009
DOI
10.1186/s12906-023-03877-1
eISSN
2662-7671
Externe Identifier
  • PubMed Central ID: PMC9930359
Ausgabe der Veröffentlichung
1
Zeitschrift
BMC Complement Med Ther
Schlüsselwörter
  • Apoptosis
  • Brucea antidysenterica
  • Cytotoxicity
  • Hydnocarpin
  • Multidrug resistance
  • Simaroubaceae
  • Humans
  • Plant Extracts
  • Methanol
  • Brucea
  • Simaroubaceae
  • Adenocarcinoma
  • Reactive Oxygen Species
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Tumor Suppressor Protein p53
  • Cell Line, Tumor
  • Antineoplastic Agents, Phytogenic
  • Drug Resistance, Neoplasm
  • Colonic Neoplasms
  • Neoplasm Proteins
  • Caspases
Sprache
eng
Country
England
Paginierung
48
PII
10.1186/s12906-023-03877-1
Datum der Veröffentlichung
2023
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Titel
Cytotoxicity of the methanol extracts and compounds of Brucea antidysenterica (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
23

Data source: PubMed

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