Complementary treatment possibilities for the therapy of cancer are increasing
in demand due to the severe side effects of the standard cytostatics used in
the first-line therapy. A common approach as a complementary treatment is the
use of aqueous extracts of Viscum album L. (Santalaceace). The therapeutic
activity of these extracts is attributed to Mistletoe lectins which are
Ribosome-inactivating proteins type II. Besides these main constituents the
extract of Viscum album L. comprises also a mixture of lipophilic ingredients
like triterpene acids of the oleanane, lupane and ursane type. However, these
constituents are not contained in commercially available aqueous extracts due
to their high lipophilicity and insolubility in aqueous extraction media. To
understand the impact of the extract ingredients in cancer therapy, the
intracellular uptake of the mistletoe lectin I (ML) by cultured tumor cells
was investigated in relation to the mistletoe triterpene acids, mainly
oleanolic acid. Firstly, these hydrophobic triterpene acids were solubilized
using cyclodextrins ("TT" extract). Afterwards, the uptake of either single
compounds (isolated ML and the aqueous "viscum" extract) or in combination
with the TT extract (ML+TT, viscumTT), was analyzed. The uptake of ML was
studied inTHP-1-, HL-60-, 143B- and Ewing TC-71-cells and determined after 30,
60 and 120 minutes by an enzyme linked immunosorbent assay which quantifies
the A-chain of the hololectin. It could be shown that the intracellular uptake
after 120 minutes amounted to 20 % in all cell lines after incubation with
viscumTT. The studies further revealed that the uptake in THP-1-, HL-60- and
Ewing TC-71-cells was independent of the addition of TT extract.
Interestingly, the uptake of ML by 143B-cells could only be measured after
addition of triterpenes pointing to resistance to mistletoe lectin