The in vitro antiproliferative activity of an aqueous mistletoe extract (
AME) with a defined content of bioactive mistletoe
lectin (ML) was tested in 25 human tumor cell lines, including 20 solid and 5
hematological malignancies and 47 human
tumor xenografts. The antiproliferative activity of
AME was compared to that of the standard
cytotoxic agent doxorubicin (CAS 23214-92-8,
adriamycin, ADR) using the sulforhodamin B,
propidium iodide and soft
agar colony forming assays, respectively.
AME was highly cytotoxic in solid human
tumors with mean IC70 values in the range of 0.17-1 ng ML/ml (2.8-17 pmol bioactive ML). On a molar basis,
AME was 3 to 4 logs more potent than ADR and showed differential cytotoxicity towards
tumors of the breast, small cell and non-small cell lung, prostate and
renal cell cancers.
AME was also highly active in
hematological malignancies with steep dose response curves resulting in mean IC70 values of 0.12 ng ML/ml (2 pmol). The
acute lymphoblastic leukemia cell line HL-60 was the most sensitive, the
histiocytic lymphoma cell line U937 the most resistant
hematological malignancy. It is important to stress that
AME did not induce a biologically relevant increase of cell proliferation in any of the tumor cell lines tested. Our data suggest that
AME has in vitro antitumor profiles similar to those of classical
anticancer agents. Clear dose-response relationships were found in all of the performed experiments and interesting differential cytotoxicity patterns were observed. Experiments with sensitive
tumor types identified in these in vitro studies are currently ongoing in order to demonstrate the anticancer activity of
AME in different animal
tumor models.