Comparison of the effects of Viscum album lectin ML-1 and fresh plant extract (Isorel) on the cell growth in vitro and tumorigenicity of melanoma B16F10.
Numerous findings indicate that specific plant lectins acting against cancer could be major active components of Viscum album extracts, although activity of low molecular weight components (peptides, carbohydrates and alkaloids) might be as essential for the beneficial activity of the plain plant extracts, too. Thus, active principle of Viscum album extracts is still not understood, and is difficult to be analysed because of the complex composition of the extracts and uncertainty of the standardised effectiveness (batch consistency) of the extracts. The aims of this study were to compare the concentration dependent effects of the pure mistletoe lectin (ML-1) with the fresh plant Viscum album extract (Isorel) and its different MW components on the in vitro growth of ConA stimulated lymphocytes, on the growth and tumorigenicity (artificial lung metastases development) of murine melanoma B16F10 cells, and to compare concentration dependent effects of the different types of the Viscum album extracts in vitro (applying novel type of MTT assay). The results obtained indicate that the effects of Isorel used at high dose could be result of toxic activity of the mistletoe lectins ("ML-1 like" activity). Unlike ML-1, if used at low concentrations, Isorel selectively inhibited tumor cells, due the activity of the low MW components. On the other hand, the number of tumor nodules was reduced (in comparison to the control) equally in the lungs of mice injected with B16F10 cells pre-treated in vitro with the plain Viscum album extract or any of its modifications or ML-1. Hence, it is supposed that the beneficial therapeutic effects of Isorel might result from the combined biological activity of the high and the low MW components not lectins only. Similarly, in MTT assay low concentrations of all types of the Viscum album extract showed stronger inhibiting activity for B16F10 and HeLa cells than pure ML-1. According to these results we propose a standardisation of aqueous Viscum album extracts by comparing their and ML-1 concentration dependent activity on the tumor cells in vitro applying MTT bioassay described which should be relevant for further evaluation of their active principle and for improvement of biotherapy of cancer.
Zarković
N
N
Rudjer Bosković Institute, Dept. of Molecular Medicine, Zagreb, Croatia. zarkovic@olimp.irb.hr
Kalisnik
T
T
Loncarić
I
I
Borović
S
S
Mang
S
S
Kissel
D
D
Konitzer
M
M
Jurin
M
M
Grainza
S
S
D000276:Adjuvants, Immunologic / Q000627:therapeutic use / Q000633:toxicity*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D037102:Lectins / Q000627:therapeutic use / Q000633:toxicity; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D014784:Mistletoe; D010936:Plant Extracts / Q000633:toxicity; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D010946:Plants, Medicinal; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000627:therapeutic use* / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000972:Antineoplastic Agents, Phytogenic; C049374:Isorel M; D037102:Lectins; D010936:Plant Extracts; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum