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Human cancer cells exhibit in vitro individual receptiveness towards different mistletoe extracts
F Knöpfl-Sidler1, A Viviani, L Rist
1Institute for Pharmaceutical Biology, University of Münster, Germany.
Abstract:
In vitro cytotoxic effects of three aqueous mistletoe extracts on cell physiology against different human tumor cell lines and primary cancer cells were investigated in order to compare the receptiveness of different cancer cells against different mistletoe products. Therefore cell proliferation (BrdU-incorporation assay), mitochondrial activity (MTT-testing) and necrotic cell toxicity (LDH assay) were assayed over serial dilutions of the test products. Data obtained with HELA-S3, MOLT-4, MFM-223, COR-L51, KPL-1 and VM-CUB1 tumor cell lines and Iscador M (20 mg/ml), Iscador Q (20 mg/ml) and Abnobaviscum Fraxini -2 (20 mg/ml) indicated significant growth-inhibition of all cell lines, but also different cell susceptibilities against the different extracts. These variations were not only monitored on established cell lines but also on primary mamma carcinoma cells from surgical resectates. Concerning cell proliferation and mitochondrial activity Abnobaviscum Fraxini exhibits stronger inhibitory effects compared to products from the Iscador series. In case the evaluation was standardized on the active contents of VAA-I within the different products, the Iscador extracts possess higher cytotoxic activity. Pure viscotoxins and mistletoe lectins exhibited less effects than the extracts. The simultaneous presence of pure mistletoe lectins and mistletoe polysaccharides diminished the VAA-mediated cytotoxic effects. The presence of fetal calf serum (FCS) in cultivation media during in vitro testing diminished the cytotoxic effects of mistletoe extracts. It was shown that in vivo application of mistletoe preparations led to the formation of antibodies against unknown compounds of the extracts, diminishing the cytotoxic effect.
Insights
Mistletoe extracts show varied cytotoxic effects on cancer cells, with Abnobaviscum Fraxini being more potent in inhibiting proliferation and mitochondrial activity. Standardized VAA-I content reveals higher activity in Iscador extracts.
Area of Science:
- Phytochemistry
- Pharmacology
- Oncology
Background:
- Mistletoe extracts are used in complementary cancer therapy.
- Understanding the differential effects of various mistletoe products on cancer cells is crucial for optimizing treatment.
- Investigating the mechanisms of action and factors influencing mistletoe's cytotoxic effects is essential.
Purpose of the Study:
- To compare the in vitro cytotoxic effects of three aqueous mistletoe extracts (Iscador M, Iscador Q, Abnobaviscum Fraxini -2) on various human tumor cell lines and primary cancer cells.
- To evaluate the receptiveness of different cancer cells to different mistletoe products.
- To analyze the impact of specific components and experimental conditions on mistletoe's efficacy.
Main Methods:
- Assessing cell proliferation using the BrdU-incorporation assay.
- Measuring mitochondrial activity via MTT assay.
- Determining necrotic cell toxicity using the LDH assay across serial dilutions of mistletoe extracts.
- Testing against established cell lines (HELA-S3, MOLT-4, MFM-223, COR-L51, KPL-1, VM-CUB1) and primary mamma carcinoma cells.
Main Results:
- All tested mistletoe extracts demonstrated significant growth inhibition across all cell lines and primary cells.
- Abnobaviscum Fraxini showed stronger inhibitory effects on cell proliferation and mitochondrial activity compared to Iscador extracts.
- When standardized for VAA-I content, Iscador extracts exhibited higher cytotoxic activity. Pure viscotoxins and lectins were less effective than extracts.
- Fetal calf serum (FCS) in culture media reduced the cytotoxic effects of mistletoe extracts. In vivo application led to antibody formation, diminishing cytotoxic effects.
Conclusions:
- Cancer cell susceptibility to mistletoe extracts varies, necessitating personalized approaches.
- Abnobaviscum Fraxini and Iscador extracts possess distinct cytotoxic profiles, offering potential for tailored cancer therapy.
- Experimental factors like FCS and in vivo antibody formation can modulate mistletoe's therapeutic efficacy, highlighting the complexity of its action.
