Differential cytotoxic properties of Helleborus niger L. on tumour and immunocompetent cells. (15th January 2015)

• Record Type: Journal Article
• Authors: Schink, Michael; Garcia-Käufer, Manuel; Bertrams, Julia; Duckstein, Sarina M.; Müller, Margit B.; Huber, Roman; Stintzing, Florian C.; Gründemann, Carsten
• Is Part Of: Journal of ethnopharmacology. Volume 159(2015)
• Page Start: 129
• Page End: 136
• Publication Date: 2015-01-15
• Subjects: AM anthroposophic medicine -- HPLC high performance liquid chromatography -- NK cells natural killer cells -- IFN-γ interferon-gamma -- PBMC peripheral blood mononuclear cells -- CD cluster of differentiation; Ranunculaceae -- Saponin -- Protoanemonin -- Lymphocytes -- Tumour therapy -- Complementary medicine -- Anthroposophical medicine; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2014.11.003
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: In Romanian folk medicine, Helleborus niger L. is used for the treatment of rheumatoid arthritis or viral infections and in complementary therapy, especially in anthroposophic medicine (AM), where the plant is administered as an adjuvant to treat malignant diseases. In the present study, we investigated the differential cytotoxic effects of H. niger on human tumour and healthy cells of the human immune system in vitro . Material and methods: Protoanemonin and saponins, as significant constituents of H. niger extracts, were quantified in five individual batches using validated HPLC methods. Further, the impact of H. niger on proliferation capacity (MTT assay) as well as on apoptosis and necrosis induction in a panel of tumour cell lines and human lymphocytes (combined annexin V and propidium iodide staining) was monitored. In addition, NK cell function (degranulation-CD107a assay and IFN-gamma secretion) was also investigated since these immunocompetent cells are important for the control of malignancies within the human body. Results: Extracts of H. niger induced proliferation inhibition not only of lymphoblastic leukaemia cells (MOLT4; IC50 : 171 µg/mL) but also of myosarcoma (SK-UT-1b; IC50 : 304 µg/mL) and melanoma cells (HT-144; IC50 : 569 µg/mL) due to the induction of apoptosis. Purified T cells or NK cells were significantly affected through the presence of high H. niger concentrations while bulk lymphocytes were not affected. NK cells' anti-tumour functions expressed by degranulation capacity as well as IFN-y production were unaffected by the presence of the H. niger extract. Since protoanemonin and saponins have been reported in the literature to exert cytotoxic effects, their content was also determined. Conclusions: H. niger extracts exhibit differential cytotoxicity towards tumour cell lines and healthy human T- and NK-cells. Graphical abstract: