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

Abstract
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.
AuthorsA M Burger, U Mengs, J B Schüler, H H Fiebig
JournalArzneimittel-Forschung (Arzneimittelforschung) Vol. 51 Issue 9 Pg. 748-57 (Sep 2001) ISSN: 0004-4172 [Print] Germany
PMID11642008 (Publication Type: Journal Article)
Chemical References
  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Intercalating Agents
  • Plant Extracts
  • Propidium
  • Doxorubicin
Topics
  • Animals
  • Antibiotics, Antineoplastic (pharmacology)
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Cell Division (drug effects)
  • Doxorubicin (pharmacology)
  • Erythrocytes (immunology)
  • Humans
  • Intercalating Agents (pharmacology)
  • Mistletoe (chemistry)
  • Neoplasm Transplantation
  • Plant Extracts (pharmacology)
  • Plants, Medicinal
  • Propidium (pharmacology)
  • Sheep (immunology)
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay

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