Cytotoxicity of the methanol extracts and compounds of Brucea antidysenterica (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines.
Humans
Plant Extracts
/ chemistry
Methanol
Brucea
Simaroubaceae
Adenocarcinoma
/ drug therapy
Reactive Oxygen Species
/ metabolism
ATP Binding Cassette Transporter, Subfamily G, Member 2
Tumor Suppressor Protein p53
Cell Line, Tumor
Antineoplastic Agents, Phytogenic
/ chemistry
Drug Resistance, Neoplasm
Colonic Neoplasms
/ drug therapy
Neoplasm Proteins
/ metabolism
Caspases
/ metabolism
Apoptosis
Brucea antidysenterica
Cytotoxicity
Hydnocarpin
Multidrug resistance
Simaroubaceae
Journal
BMC complementary medicine and therapies
ISSN: 2662-7671
Titre abrégé: BMC Complement Med Ther
Pays: England
ID NLM: 101761232
Informations de publication
Date de publication:
15 Feb 2023
15 Feb 2023
Historique:
received:
08
09
2022
accepted:
08
02
2023
entrez:
16
2
2023
pubmed:
17
2
2023
medline:
18
2
2023
Statut:
epublish
Résumé
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. 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. 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 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.
Sections du résumé
BACKGROUND
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
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
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 IC
CONCLUSION
CONCLUSIONS
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.
Identifiants
pubmed: 36793009
doi: 10.1186/s12906-023-03877-1
pii: 10.1186/s12906-023-03877-1
pmc: PMC9930359
doi:
Substances chimiques
hydnocarpin
51419-48-8
Plant Extracts
0
Methanol
Y4S76JWI15
Reactive Oxygen Species
0
ATP Binding Cassette Transporter, Subfamily G, Member 2
0
Tumor Suppressor Protein p53
0
Antineoplastic Agents, Phytogenic
0
Neoplasm Proteins
0
Caspases
EC 3.4.22.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
48Informations de copyright
© 2023. The Author(s).
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