Antiproliferative activity of an aqueous mistletoe extract in human tumor cell lines and xenografts in vitro

The in vitro antiproliferative activity of an aqueous mistletoe extract (AM E) with a defined content of bioactive mistletoe lectin (ML) was tested in 25 human tumor cell lines, including 20 solid and 5 hematological malignanc ies and 47 human tumor xenografts. The antiproliferative activity of AME wa s 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 soli d 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 t han ADR and showed differential cytotoxicity towards tumors of the breast, small cell and non-small cell lung, prostate and renal cell cancers. AME wa s 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 histiocy tic lymphoma cell line U937 the most resistant hematological malignancy. It Is important to stress that AME did not induce a biologically relevant inc rease 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 foun d in all of the performed experiments and Interesting differential cytotoxi city patterns were observed. Experiments with sensitive tumor types identif ied in these in vitro studies are currently ongoing in order to demonstrate the anticancer activity of AME in different animal tumor models.