In vitro screening of plant extracts traditionally used as cancer remedies in Ghana – 15-Hydroxyangustilobine A as the active principle in Alstonia boonei leaves. (30th January 2021)

• Record Type: Journal Article
• Authors: Spiegler, Verena; Greiffer, Luise; Jacobtorweihen, Joshua; Asase, Alex; Lanvers-Kaminsky, Claudia; Hempel, Georg; Agyare, Christian; Hensel, Andreas
• Is Part Of: Journal of ethnopharmacology. Volume 265(2020)
• Publication Date: 2021-01-30
• Subjects: Alstonia boonei -- Paullinia pinnata -- Cancer -- Medicinal plants -- 15-Hydroxyangustilobine A -- Vallesamine; 7-AAD 7-Aminoactinomycin D -- DMSO dimethyl sulfoxide -- EtOAc ethyl acetate -- FCPC fast centrifugal partition chromatography -- FCS fetal calf serum -- FITC fluorescein isothiocyanate -- HRESI-MS high resolution electrospray ionization mass spectrometry -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide -- NC negative control -- PBS phosphate buffered saline -- PC positive control; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2020.113359
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Cancer represents a major health burden and drain on the global healthcare systems. Traditional African medicine widely use a variety of plant species for treatment of different kinds of cancer. A previous systematic survey by traditional healers in the Ashanti region of Ghana revealed a good overview on the plant species and herbal materials used for the different types of cancer. Aims of the study: The following study aimed to investigate 18 herbal materials from 10 plant species based on the cancer survey in Ghana regarding potential cytotoxicity against different cancer cell lines under in vitro conditions followed by subsequent bioassay-guided fractionation towards the active principle. Materials and methods: Ethanol-water (1:1) extracts were tested (1–100 μg/mL) against a panel of cancer cell lines according to their respective traditional use. Selected extracts with relevant cytotoxicity in this screening were also tested against common pediatric malignancies (leukemias (HL-60, REH) and Ewing sarcoma (RD-ES and CADO-ES1)). Bioassay-guided fractionation of the hydroalcoholic extract from Alstonia boonei was performed by liquid-liquid chromatography and preparative HPLC. Preliminary mechanistic studies on the mode of action were performed by flow cytometric cell cycle analysis as well as apoptosis and necrosis staining. Results: Screening of plant extracts revealed relevant cytotoxicity against all tested cancer cell lines for Alstonia boonei leaves and stem of Paulinia pinnata . The A. boonei extract was additionally found to be active against common pediatric tumor types (leukemias and Ewing sarcoma). Bioassay-guided fractionation of the A. boonei extract revealed the presence of 15-hydroxyangustilobine A 1 as the active principle (IC50 26 μM against MCF-7 cells). This is the first report of this compound in A. boonei . 1 was shown to lead to cell cycle arrest in the G2/M-phase (MCF-7 cells), triggering cells at least partially into apoptosis. Conclusion: In summary, an appreciable in vitro activity was revealed for the leaf extract from A. boonei and the isolated vallesamine type indole alkaloid 1, which has to be investigated in future studies towards a potential clinical use. Graphical abstract: Image 1