article · BMC Complementary Medicine and Therapies
Malignant cells frequently develop resistance to existing therapies, limiting cancer survival rates. Brucea antidysenterica, an African medicinal plant traditionally used against several ailments including cancer, was examined to identify cytotoxic constituents capable of combating drug-resistant cancer cell lines. Seven phytochemicals were extracted and identified from the leaves and stems. Crude leaf extracts alongside two isolated compounds, an indole derivative and hydnocarpin, showed antiproliferative effects across nine human cancer cell lines. Hydnocarpin proved particularly potent, and drug-resistant cancer cells displayed hypersensitivity to it. Further testing revealed that both the leaf extract and hydnocarpin trigger programmed cell death in leukaemia cells through caspase activation, disruption of mitochondrial membrane potential, and the elevation of reactive oxygen species. These findings indicate that compounds from Brucea antidysenterica, especially hydnocarpin, represent promising natural candidates for the development of treatments targeting drug-resistant cancers.
Drug resistance remains a critical challenge in modern oncology, frequently causing chemotherapy to fail. Demonstrating that compounds from traditionally used African flora can effectively kill resistant cancer cells opens new avenues for therapeutic discovery. Uncovering how these natural molecules trigger tumour cell death supports the search for alternative cancer treatments capable of overcoming existing drug limitations.
This research is at an early, laboratory-based discovery stage, tested solely on human cancer cell lines in vitro. The findings could potentially enable pharmaceutical developers and oncology researchers to explore hydnocarpin and related extracts as starting points for drug leads against drug-resistant tumours. Substantial further research, including extensive preclinical and clinical validation, remains necessary before any commercial or therapeutic application can be realised.
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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))1 H indole ( 1 ) and hydnocarpin ( 2 ), as well as the reference compound, doxorubicin, had antiproliferative activity against 9 cancer cell lines. The IC 50 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.
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DOI: 10.1186/s12906-023-03877-1
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