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Anti tumor effects of standard- and triterpenoid enriched mistletoe extracts on murine melanomas
The European mistletoe (Viscum album L.) contains a variety of water soluble (mistletoe lectins, viscotoxins) and -insoluble (triterpenoids) substances with anti-cancer effects. This makes mistletoe derived extracts and compounds interesting for treatment of cancers with low response rates like melanoma. Mistletoe therapy is the most important complementary therapy in central Europe (1) but up to date the standard preparations contain only water soluble substances of the plant. Triterpenoid extracts from mistletoe (80% oleanolic acid and 4% betulinic acid) are well characterized (2) and solubilization with 2-hydroypropyl-beta-cyclodextrin makes them available for cell culture experiments and cancer treatment in animal models as so called solubilized triterpene extracts (STE).
Experimental setup: B16.F10 melanoma cells were inoculated subcutaneous (sc) into the flanks of C57BL/6 mice. Treatment with mistletoe extracts (sc injections) were started three days after tumor inoculation for ten cycles (every second day). The tumor size was determined by calliper measurement every second day.
We show here, that high dose mistletoe treatment slows down melanoma growth and prolongs survival of the treated animals. Mistletoe extracts containing STE are more effective in treating melanoma than normal extracts. Histological examinations of the tumors and surrounding tissue show increased tumor necrosis, infiltrating immune cells in the tumor surrounding tissue and decreased neoangiogenesis compared to control animals.
We show here, that standard mistletoe extracts show anti-cancer effects on melanoma. Interestingly, novel mistletoe preparations containing STE from mistletoe in addition to the water soluble substances show improved anti-cancer effects.
Acknowledgements: Software AG Stiftung, Darmstadt, Germany.
References: 1. Horneber, M.A. et al. (2008) Cochrane Database Syst Rev 2:CD003297.
2. Jäger, S. et al. (2009) Molecules 14:2016–31.