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

• Published in: BMC complementary and alternative medicine 2023-02, Vol.23 (1), p.48-48, Article 48
• Main Authors: Youmbi, Laetitia M, Makong, Yves S D, Mbaveng, Armelle T, Tankeo, Simplice B, Fotso, Ghislain W, Ndjakou, Bruno L, Wansi, Jean D, Beng, Veronique P, Sewald, Norbert, Ngadjui, Bonaventure T, Efferth, Thomas, Kuete, Victor
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic drugs; Antiproliferatives; Antitumor agents; Apoptosis; Asthma; ATP Binding Cassette Transporter, Subfamily G, Member 2; Brucea; Brucea antidysenterica; Cancer therapies; Caspase; Caspases - metabolism; Cell activation; Cell cycle; Cell Line, Tumor; Chromatography; Cloning; Colon cancer; Colonic Neoplasms - drug therapy; Column chromatography; Constituents; Cytotoxicity; Diarrhea; Doxorubicin; Drug discovery; Drug resistance; Drug resistance in microorganisms; Drug Resistance, Neoplasm; Drug therapy; Dysentery; Flow cytometry; Global health; Health aspects; Herbal medicine; Humans; Hydnocarpin; Hypersensitivity; Iodides; Leukemia; Life expectancy; Life span; Malaria; Medicinal plants; Medicine, Botanic; Medicine, Herbal; Membrane potential; Methanol; Mitochondria; Multidrug resistance; Neoplasm Proteins - metabolism; Neoplasm Proteins - pharmacology; Phytochemicals; Plant Extracts - chemistry; Propidium iodide; Public health; Reactive oxygen species; Reactive Oxygen Species - metabolism; Simaroubaceae; Staining; Toxicity; Tumor cell lines; Tumor proteins; Tumor Suppressor Protein p53; Tumors; Vector-borne diseases; Waterborne diseases; World health
• ISSN: 2662-7671; 2662-7671; 1472-6882
• DOI: 10.1186/s12906-023-03877-1

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 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. BAL and its constituents, mostly compound 2, are potential antiproliferative products from Brucea antidysenterica. Other studies will be