Recombinant mistletoe lectin (rML) is successful in treating human ovarian cancer cells transplanted into severe combined immunodeficient (SCID) mice.
The main active constituents carrying the anti-cancer activities of aqueous mistletoe extracts have recently been identified as the mistletoe lectins (MLs). Although three different isolectins have been isolated from plant extracts, molecular biological techniques have revealed the presence of one gene only. Subsequently, recombinant mistletoe lectin (rML) has become available and the aim of the present study was to analyse its anti-cancer potential. SoTü 3 human ovarian cancer cells (2x10(7)) were injected intraperitoneally into SCID mice, while rML treatment was started on the following day. Three experimental groups (n=20 SCID mice) each received every working day an intraperitoneal injection of 30, 150, 500 ng rML per kg body weight, respectively, while 20 SCID mice in the control group received the vehicle solution only. The survival of the animals was taken as the principal outcome measure. In addition, the peritoneal cavity was searched for the presence of tumour cells. Animals were sacrificed when the weight increase due to the development of ascites exceeded 120% of the initial body weight. The treatment continued until day 83 and the surviving animals were sacrificed 84 days after inoculation. In the control group, only two animals survived and were free of tumour at the end of the experiment at 84 days. In contrast, thirteen animals in the 500 ng/kg rML group were still alive and no evidence for the presence of tumour cells in the peritoneum was found. Both, number of animals surviving and survival time were larger in this treatment group. The 30 ng/kg rML group showed an increased number of survivors, whilst the 150 ng rML per kg body weight group revealed the worst survival rates. The results of the present study indicate that rML has potent anti-tumour activity, if administered locally into the peritoneum of a human ovarian cancer harbouring SCID mouse. RML is a macromolecule and its instillation into the peritoneal cavity seems to be particularly effective to inhibit intraperitoneal growth of cancer cells. One explanation might be that altered glycosylation of the cancer cells leads to an increased affinity of rML towards tumour cells. Clinical studies with post-operative instillation of rML in ovarian cancer patients should, therefore, be encouraged to provide clinical evidence for the effectiveness of rML treatment.
Schumacher
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Department of Anatomy, University Hospital Eppendorf, Martinistrasse 52, D-20246, Hamburg, FRG. uschumac@uke.uni-hamburg.de
Feldhaus
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Mengs
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D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D028321:Plant Preparations; D010940:Plant Proteins; D011994:Recombinant Proteins / Q000627:therapeutic use; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D028321:Plant Preparations; D010940:Plant Proteins; D011994:Recombinant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum