In-vitro-Untersuchungen zur Hemmung der Angiogenese und der Tumorzellmigration durch einen wässrigen Extrakt aus Viscum album ssp. album, Mali

Zusammenfassung

Hintergrund und Ziel Mistelpräparate, insbesondere aus der Apfelbaummistel (Viscum album ssp. album, Mali), werden häufig von Mammakarzinom-Patientinnen als komplementäre Therapiemaßnahme nach Resektion, Chemo- oder Radiotherapien angewendet. In klinischen Studien wurde bereits der Nutzen von Mistelpräparaten nachgewiesen. Da die dahinter liegenden Wirkmechanismen bisher nicht vollständig aufgeklärt sind, sollten die potenziell antitumoralen Effekte eingehender untersucht werden.

Material und Methoden Es wurden In-vitro-Untersuchungen zu den Effekten eines wässrigen Extrakts aus Viscum album ssp. album, Mali (Iscucin^® Mali) auf die Zellviabilität, auf verschiedene Phasen der Angiogenese (Zellproliferation und Kapillarausbildung) sowie auf die Zellmigration humaner Tumorzellen durchgeführt.

Ergebnisse Zwei verschiedene Assays gaben Hinweise auf antiproliferative Effekte mit einer halbmaximalen Hemmung bei Konzentrationen<100 µg/ml. Es zeigten sich außerdem hemmende Effekte auf die Kapillarausbildung. Die Migrationsfähigkeit verschiedener Tumorzelllinien wurde durch Iscucin^® Mali mit unterschiedlicher Effektivität gehemmt, vergleichbar mit der Referenzsubstanz Bosutinib bei den Zelllinien LN229, SK-N-SH, DLD-1, HeLa und etwas besser bei Caki-2.

Diskussion und Schlussfolgerung Ein Panel aus verschiedenen Untersuchungsmethoden zeigte in Abhängigkeit von der Zelllinie antitumorale Effekte von Iscucin^® Mali, vor allem im Bereich der Kapillarausbildung und der Zellmigration. Dies lässt vermuten, dass sowohl das Tumorwachstum als auch die Metastasierung verzögert werden können. Weitere Studien sind erforderlich, um die Relevanz der gewonnenen Daten im klinischen Bereich zu untermauern.

Abstract

Purpose Mistletoe preparations are commonly used in the treatment of breast cancer as complementary therapy after resection, chemotherapy or radiotherapy. Most frequently, a preparation of the mistletoe from the apple tree is applied (Viscum album ssp. album, Mali). A benefit of mistletoe preparations has been shown in clinical studies though the underlying mechanism of action is not fully clarified so far. Therefore the aim of the study was to evaluate the potentially anti-tumoral effects in detail.

Material and Methods In vitro investigations evaluating the effects of an aqueous extract of Viscum album ssp. album, Mali (Iscucin^® Mali) on cell viability, cell proliferation and tube formation in a two-dimensional and three-dimensional design, as well as tumor cell migration were performed.

Results Two different assays provided an indication for antiproliferative effects with an IC₅₀ of less than 100 µg/ml. 309 µg/ml Iscucin^® Mali and 500 µg/ml 5-fluorouracil (5-FU) reduced human endothelial cells proliferation by 90%. 500 µg/ml Iscucin^® Mali inhibited cell growth almost completely (96.8%). Iscucin^® Mali revealed also an inhibitory action on tube formation. 2.000 µg/ml Iscucin^® Mali yielded more than 50% inhibition of cell migration of most cell lines tested in the present study. The intensity of effects was dependent on the respective cell lines. The inhibition of cell migration capacity by Iscucin^® Mali was comparable with the reference substance Bosutinib for cell line LN229, SK-N-SH, DLD-1, Caki-2 and HeLa. The mamma carcinoma cell line MCF-7 and MDA-MB-231 as well as A437 (squamous cell carcinoma) and U87-MG (glioblastoma) did not respond. The strongest effects were shown for Caki-2 (renal cell carcinoma) and SK-N-SH (neuroblastoma).

Discussion and Conclusion A panel of different assays showed an anti-tumoral effect of Iscucin^® Mali depending on cell line, especially on tube formation and cell migration. It is therefore assumed that this mistletoe preparation has an impact on tumor growth and retards the progression of disease or metastasis. Further studies are necessary to investigate these effects on a clinical scale.

Schlüsselwörter

Angiogenese - Zellmigration - Tumor - Kapillarausbildung - Mistel

Key words

Angiogenesis - cell migration - cancer - tube formation - mistletoe

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