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

BMC Complementary Medicine and Therapies

Research

Laetitia M. Youmbi¹  Simplice B. Tankeo²  Armelle T. Mbaveng²  Victor Kuete²  Veronique P. Beng³  Jean D. Wansi⁴  Yves S. D. Makong⁴  Bruno L. Ndjakou⁵  Bonaventure T. Ngadjui⁶  Ghislain W. Fotso⁶  Thomas Efferth⁷  Norbert Sewald⁸ 

[1] Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon;Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon;Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon;Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, University of Mainz, Staudinger Weg 5, 55128, Mainz, Germany;Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon;Department of Chemistry, Faculty of Science, University of Douala, Douala, Cameroon;Department of Chemistry, Higher Teacher Training College, University of Yaoundé 1, Yaounde, Cameroon;Department of Organic Chemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon;Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, University of Mainz, Staudinger Weg 5, 55128, Mainz, Germany;Organic and Bioorganic Chemistry, Faculty of Chemistry, Bielefeld University, 33501, Bielefeld, Germany;

关键词: Apoptosis;    Brucea antidysenterica;    Cytotoxicity;    Multidrug resistance;    Hydnocarpin;    Simaroubaceae;   

DOI  :  10.1186/s12906-023-03877-1

 received in 2022-09-08, accepted in 2023-02-08,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCancer 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.MethodsSeven 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.ResultsPhytochemical 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.ConclusionBAL 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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