Home LiteratureArticle Details
PMID: 18026191 Published · ppublish English Journal Article

Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model.

British journal of cancer ·Vol. 98 ·No. 1 ·2008-01-15 ·Pages 106-12

Thies A, Dautel P, Meyer A, Pfüller U, Schumacher U

Abstract

This study investigates the effects of mistletoe lectin-I (ML-I) on melanoma growth and spread in vivo. The human melanoma cell line MV3 was xenografted into severe combined immunodeficient mice and vehicle solution or purified ML-I was administered at 30, 150 and 500 ng per kg body weight (20 mice per group) daily. After 19 days, mice were killed, primary tumours (PTs) and lungs were dissected out, and tumour weights, number of lung metastases (LMs), number of tumour-infiltrating dendritic cells (DCs), and apoptosis rates in the melanoma cells and in the DCs were assessed. A 35% reduction of PT weight (P=0.03) and a 55% decrease in number of LMs (P=0.016) were evident for low-dose ML-I (30 ng kg(-1)) treatment but not for higher doses. Mistletoe lectin-I increased apoptosis rates in the melanoma cells of PTs at all doses, while no induction of apoptosis was noted in the LMs. Low-dose ML-I significantly increased the number of DCs infiltrating the PTs (P<0.0001) and protected DCs against apoptosis, while higher doses induced apoptosis in the DCs (P<0.01). Our results demonstrate that low-dose ML-I reduced melanoma growth and number of metastases in vivo, primarily due to immunomodulatory effects.

MeSH Terms
Animals Apoptosis/drug effects Dendritic Cells/drug effects,metabolism,pathology Humans Lung Neoplasms/drug therapy,metabolism,secondary Lymphocytes, Tumor-Infiltrating Male Melanoma, Experimental/drug therapy,metabolism,pathology Mice Mice, Inbred BALB C Mice, SCID Plant Preparations/administration & dosage Plant Proteins/administration & dosage Ribosome Inactivating Proteins, Type 2/administration & dosage Toxins, Biological/administration & dosage Transplantation, Heterologous Tumor Cells, Cultured
Chemicals
Plant Preparations Plant Proteins Ribosome Inactivating Proteins, Type 2 Toxins, Biological mistletoe lectin I
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Thies A
Zentrum für Experimentelle Medizin, Institut für Anatomie II: Experimentelle Morphologie, Universitätsklinikum Hamburg Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. thies@uke.uni-hamburg.de
Dautel P
Meyer A
Pfüller U
Schumacher U
References (36)
36 references, click to expand
  1. Inhibitory effect of Korean mistletoe (Viscum album coloratum) extract on tumour angiogenesis and metastasis of haematogenous and non-haematogenous tumour cells in mice.
    Cancer Lett. 1995 Oct 20;97(1):83-91 PMID: 7585483
  2. Quantitative assessment of spontaneous lung metastases of human HT29 colon cancer cells transplanted into SCID mice.
    Cancer Lett. 2000 May 1;152(2):151-6 PMID: 10773406
  3. The development of stable protein formulations: a close look at protein aggregation, deamidation, and oxidation.
    Crit Rev Ther Drug Carrier Syst. 1993;10(4):307-77 PMID: 8124728
  4. Clinical relevance of immunoactive mistletoe lectin-I.
    Anticancer Drugs. 1997 Apr;8 Suppl 1:S53-5 PMID: 9179369
  5. Macrophages and their subpopulations following allogenic bone marrow transplantation for chronic myeloid leukaemia.
    Virchows Arch. 2000 Aug;437(2):160-6 PMID: 10993276
  6. Suppression of growth of tumour cell lines in vitro and tumours in vivo by mistletoe lectins.
    Histol Histopathol. 2006 Mar;21(3):285-99 PMID: 16372250
  7. Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials.
    Lancet Oncol. 2003 Dec;4(12):748-59 PMID: 14662431
  8. Phase I/II study of treatment with dendritic cell vaccines in patients with disseminated melanoma.
    Cancer Immunol Immunother. 2004 Feb;53(2):125-34 PMID: 14600790
  9. Clinically proven markers of metastasis predict metastatic spread of human melanoma cells engrafted in scid mice.
    Br J Cancer. 2007 Feb 26;96(4):609-16 PMID: 17262079
  10. Mistletoe extract standardized for the galactoside-specific lectin (ML-1) induces beta-endorphin release and immunopotentiation in breast cancer patients.
    Anticancer Res. 1994 May-Jun;14(3B):1339-42 PMID: 8067703
  11. Inhibition of tumor growth and metastasis by Korean mistletoe lectin is associated with apoptosis and antiangiogenesis.
    Cancer Biother Radiopharm. 2001 Oct;16(5):439-47 PMID: 11776761
  12. Local administration of granulocyte/macrophage colony-stimulating factor increases the number and activation state of dendritic cells in the sentinel lymph node of early-stage melanoma.
    Cancer Res. 2004 Nov 15;64(22):8456-60 PMID: 15548718
  13. Glycoconjugate profiling of primary melanoma and its sentinel node and distant metastases: implications for diagnosis and pathophysiology of metastases.
    Cancer Lett. 2007 Apr 8;248(1):68-80 PMID: 16822608
  14. Binding of mistletoe lectins to cutaneous malignant melanoma: implications for prognosis and therapy.
    Anticancer Res. 2001 Jul-Aug;21(4B):2883-7 PMID: 11712781
  15. Glycoconjugate with terminal galactose. A selective property of macrophages in developing rat lung.
    Histochemistry. 1989;91(1):61-7 PMID: 2925449
  16. Influence of mistletoe lectins and cytokines induced by them on cell proliferation of human melanoma cells in vitro.
    Toxicology. 2005 Feb 1;207(1):105-16 PMID: 15590126
  17. Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins.
    Cancer Lett. 1996 Jan 19;99(1):59-72 PMID: 8564930
  18. Modulatory potency of the beta-galactoside-specific lectin from mistletoe extract (Iscador) on the host defense system in vivo in rabbits and patients.
    Cancer Res. 1989 Sep 1;49(17):4803-8 PMID: 2758413
  19. [Efficacy and safety of long-term complementary treatment with standardized European mistletoe extract (Viscum album L.) in addition to the conventional adjuvant oncologic therapy in patients with primary non-metastasized mammary carcinoma. Results of a multi-center, comparative, epidemiological cohort study in Germany and Switzerland].
    Arzneimittelforschung. 2004;54(8):456-66 PMID: 15460213
  20. Differences in the apoptosis-inducing properties of Viscum album L. extracts.
    Anticancer Drugs. 1997 Apr;8 Suppl 1:S9-14 PMID: 9179360
  21. A nonradioactive assay for ribosome-inactivating proteins.
    Anal Biochem. 1996 Dec 1;243(1):150-3 PMID: 8954537
  22. What is new in melanoma research? Vaccines, Basic and Translational Research in 2003: report of a workshop at the Third Research Meeting on Melanoma, Milan, Italy, May 2003.
    Melanoma Res. 2004 Aug;14(4):241-3 PMID: 15305152
  23. The relationship between hypoxia and angiogenesis.
    Semin Radiat Oncol. 2004 Jul;14(3):215-21 PMID: 15254864
  24. Effects of a standardized mistletoe preparation on metastatic B16 melanoma colonization in murine lungs.
    Arzneimittelforschung. 1998 May;48(5):497-502 PMID: 9638318
  25. The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial.
    Eur J Cancer. 2001 Jan;37(1):23-31 PMID: 11165126
  26. Dead or alive: immunogenicity of human melanoma cells when presented by dendritic cells.
    Cancer Res. 2000 Nov 15;60(22):6441-7 PMID: 11103811
  27. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
    Br J Cancer. 1972 Aug;26(4):239-57 PMID: 4561027
  28. Ribosome-inactivating proteins from plants.
    Biochim Biophys Acta. 1993 Dec 21;1154(3-4):237-82 PMID: 8280743
  29. Mistletoe in cancer - a systematic review on controlled clinical trials.
    Eur J Med Res. 2003 Mar 27;8(3):109-19 PMID: 12730032
  30. Assessing apoptosis: a critical survey.
    Endocr Relat Cancer. 1999 Mar;6(1):3-8 PMID: 10732778
  31. Immunomodulatory effects of Viscum album agglutinin-I on natural immunity.
    Anticancer Drugs. 1997 Apr;8 Suppl 1:S43-6 PMID: 9179367
  32. Melanoma cell-derived factors stimulate glycosaminoglycan synthesis by fibroblasts cultured as monolayers and within contracted collagen lattices.
    Br J Dermatol. 2001 Mar;144(3):465-70 PMID: 11260000
  33. Lectins isolated from Korean mistletoe (Viscum album coloratum) induce apoptosis in tumor cells.
    Cancer Lett. 1999 Feb 8;136(1):33-40 PMID: 10211936
  34. Oncopharmacological Perspectives of a Plant Lectin (Viscum album Agglutinin-I): Overview of Recent Results from In vitro Experiments and In vivo Animal Models, and Their Possible Relevance for Clinical Applications.
    Evid Based Complement Alternat Med. 2005 Mar;2(1):59-67 PMID: 15841279
  35. Humoral immune response against melanoma antigens induced by vaccination with cytokine gene-modified autologous tumor cells.
    Int J Cancer. 2004 Jan 10;108(2):307-13 PMID: 14639620
  36. Recombinant mistletoe lectin (rML) is successful in treating human ovarian cancer cells transplanted into severe combined immunodeficient (SCID) mice.
    Cancer Lett. 2000 Mar 31;150(2):171-5 PMID: 10704739
Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
Published
2008-01-15
Epub
2007-00-20
Pages
106-12
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2359693
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com