In-vitro-Untersuchungen zur Weidenmistel an verschiedenen humanen Tumorzelllinien

Zusammenfassung

Traditionell werden pharmazeutische Zubereitungen der Weidenmistel häufig bei der Therapie von Blasen- und Nierenzellkarzinomen eingesetzt. Dennoch existieren bislang nur wenige wissenschaftliche Untersuchungen zu Wirkmechanismen von Weidenmistelpräparaten. Daher wurde mithilfe verschiedener Testverfahren die Hemmung der Viabilität von Tumorzellen durch den Weidenmistelextrakt Iscucin^® Salicis bestimmt und die beteiligten Mechanismen untersucht. Des Weiteren wurde die Hemmung der Zellmigration analysiert.

Ergebnisse Der Extrakt hemmte Zellwachstum und -migration in vitro, wobei die Sensitivität der einzelnen Tumorzelllinien variierte. Vor allem sprachen neuroepitheliale Tumorzellen und Bronchialkarzinomzellen gut an. Zudem wurden pro-apoptotische Marker aktiviert. Klinische Untersuchungen stehen aus, um zu klären, bei welchen Tumoren das größte Potenzial für eine Behandlung mit Iscucin^® Salicis besteht.

Abstract

Traditionally, pharmaceutically produced mistletoe preparations from willow tree are often used for treating bladder and renal cell carcinomas. However, only little data from preparations from willow mistletoe have been published so far and the underlying mechanisms are not completely known. The inhibitory effects of an extract from mistletoe from willow tree (Iscucin^® Salicis) on the viability of cancer cells and feasible mechanisms were investigated using different assays. Furthermore, the inhibition of cell migration was analysed.

Results The extract inhibited cell growth and migration in vitro, with varying intensity depending on the respective cell line. Especially neuro-epithelial tumor cells and bronchial carcinoma cells showed a good response. Moreover, pro-apoptotic markers were activated. Clinical investigations should clarify, which types of cancer have the highest potential for a treatment with Iscucin^® Salicis.

Schlüsselwörter

Viscum album L. - Mistel - Iscucin^® Salicis - antitumoral - Zellviabilität - Apoptose

Keywords

Viscum album L. - mistletoe - Iscucin^® Salicis - anti-tumor - cell viability - apoptosis

• Literatur

• 1 Beztsinna N, de Matos MB, Walther J. et al. Quantitative analysis of receptor-mediated uptake and pro-apoptotic activity of mistletoe lectin-1 by high content imaging. Sci Rep 2018; 8: 2768-2778 . doi:10.1038/s41598-018-20915-y
• 2 Büssing A, Schietzel M. Apoptosis-inducing properties of Viscum album L. extracts from different host trees, correlate with their content of toxic mistletoe lectins. Anticancer Res 1999; 19: 23-28
• 3 Cummings BS, Wills LP, Schnellmann RG. Measurement of cell death in mammalian cells. Curr Protoc Pharmacol 2004; 25 , 12.8.1-12.8.22
• 4 Dziedzic A, Kubina R, Kabała-Dzik A. et al. Induction of cell cycle arrest and apoptotic response of head and neck squamous carcinoma cells (Detroit 562) by caffeic acid and caffeic acid phenethyl ester derivative. Evid Based Complement Alternat Med 2017; 6793456 . doi:10.1155/2017/6793456
• 5 Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 35: 495-516
• 6 Gärtner T, Link K, Müller MB. et al. Phenolic profiles of Viscum album L. subspecies from different host trees. In: Scheer R, Alban S, Becker H, Beer AM, Blaschek W, Kreis W, Matthes H, Schilcher H, Spahn G, Stange R. eds. Die Mistel in der Tumortherapie 4. Essen: KVC Verlag; 2016: 87-96
• 7 Gough W, Hulkower Kl, Lynch R. et al. A quantitative, facile, and high throughput image-based cell migration method is a robust alternative to the scratch assay. J Biomol Screen 2011; 16: 155-163
• 8 HAB. Homöopathisches Arzneibuch, Vs 38. Stuttgart: Deutscher Apotheker Verlag; 2016
• 9 Heidecke H, Meyer U. Iscucin^®-Wirkung auf die Angiogenese in vitro. Der Merkurstab 2005; 58: 302-304
• 10 HMPC. Assessment Report on Viscum album L., herba. London: European Medicines Agency (EMA), Committee on Herbal Medicinal Products (HMPC); 2012
• 11 Keepers YP, Pizao PE, Peters GJ. et al. Comparison of the sulforhodamine-B protein and tetrazolium (MTT) assays for in vitro chemosensitivity testing. Eur J Canc Clin Oncol 1991; 27: 897-900
• 12 Kohl M, Bäcker C, Wurster M. et al. Comparative investigation of monosaccharides and sugar alcohols in mistletoes (Viscum album L.) from different host trees. In: Scheer R, Alban S, Becker H, Blaschek W, Kemper FH, Kreis W, Matthes H, Schilcher H, Stange R. , eds. Die Mistel in der Tumortherapie 3. Essen: KVC Verlag; 2013: 67-76
• 13 Novais-Cruz M, Alba Abad M, van IJcken WF. et al. Mitotic progression, arrest, exit or death relies on centromere structural integrity, rather than de novo transcription. eLife 2018; 7: e36898 . doi:10.7554/eLife.36898
• 14 Park Y, Do YR, Jang B. Apoptosis of K562 leukemia cells by Abnobaviscum F^®, a European mistletoe extract. Oncology Reports 2012; 28: 2227-2232
• 15 Präbst K, Engelhardt H, Ringgeler S. et al. Basic colorimetric proliferation assays: MTT, WST, and Resazurin. Methods Mol Biol 2017; 1601: 1-17 . doi:10.1007/978-1-4939-6960-9_1
• 16 von Schoen-Angerer T, Wilkens J, Kienle GS. et al. High-dose Viscum album extract treatment in the prevention of recurrent bladder cancer: a retrospective case series. Perm J 2015; 19: 76-83 . doi:10.7812/TPP/15-018
• 17 Seifert G, Jesse P, Laengler A. et al. Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro. Cancer Lett 2008; 264: 218-228
• 18 Tsao SM, Hsia TC, Yin MC. Protocatechuic acid inhibits lung cancer cells by modulating FAK, MAPK, and NF-kB pathways. Nutr Cancer 2014; 66: 1331-1341
• 19 Urech K, Ramm H. Die Polarität der Mistel. Der Merkurstab 1997; 50: 157-168
• 20 Vanden Berghe T, Grootjans S, Goossens V. et al. Determination of apoptotic and necrotic cell death in vitro and in vivo. Methods 2013; 61: 117-129
• 21 Wilkens J. Die Weidenmistel beim Blasenkarzinom. Der Merkurstab 2007; 60: 446-449
• 22 Wilkens J. Aspirin ist gut, die Weidenmistel ist besser. zkm – Zeitschrift für Komplementärmedizin 2015; 6: 38-39
• 23 Wilkens J, Böhm G. Misteln. Aarau und München: AT Verlag; 2016: 141-151
• 24 Wilkins LR, Brautigan DL, Wu H. et al. Cinnamic acid derivatives enhance the efficacy of transarterial embolization in a rat model of hepatocellular carcinoma. Cardiovasc Intervent Radiol 2016; 40: 430-437
• 25 Wurster M, Albrecht S, Lindequist U, Stintzing F. Comparative investigation of nucleosides in mistletoes (Viscum album L.) from different host trees. In: Scheer R, Alban S, Becker H, Beer AM, Blaschek W, Kreis W, Matthes H, Schilcher H, Spahn G, Stange R. eds. Die Mistel in der Tumortherapie 4. Essen: KVC Verlag; 2016: 77-85
• 26 Xue N, Zhou Q, Ji M. et al. Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype. Sci Rep 2017; 7: 39011 . doi:10.1038/srep39011
• 27 Zuzak T, Rist L, Viviani A. et al. Das Mistelpräparat Iscucin^® – Herstellung, Analytik, Wirkung in vitro. Der Merkurstab 2004; 57: 467-473