br F Li T Li W Cao
 F. Li, T. Li, W. Cao, et al. Near-infrared light stimuli-responsive synergistic therapy nanoplatforms based on the coordination of tellurium-containing block polymer and cisplatin for cancer treatment. Biomaterials. 133 (2017) 208–218.  D. Yang, W. Luo, J. Wang, et al. A novel controlled release formulation of the Pin1 inhibitor ATRA to improve liver cancer therapy by simultaneously blocking mul-tiple cancer pathways. J. Control. Release 269 (2018) 405–422.
 T. Etrych, T. Mrkvan, P. Chytil, et al. N-(2-hydroxypropyl) methacrylamide-based polymer conjugates with pH-controlled activation of doxorubicin. I. New synthesis, physicochemical characterization and preliminary biological evaluation. J. Appl.
 T. Mrkvan, M. Sirova, T. Etrych, et al. Chemotherapy based on HPMA copolymer conjugates with pH-controlled release of doxorubicin triggers anti-tumor immunity. J. Control. Release 1 (2005) 119–129.
 D.D. Hawn, B.M. DeKoven, Deconvolution as a correction for photoelectron in-elastic energy losses in the core level XPS spectra of iron oxides, Surf. Interface Anal. 10 (1987) 63–74.
Contents lists available at ScienceDirect
Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jethpharm
Antiproliferative potential from aqueous Viscum album L. preparations and T their main constituents in comparison with ricin and purothionin on human cancer cells
Jennifer E. Felenda, Claudia Turek, Florian C. Stintzing∗
WALA Heilmittel GmbH, Dorfstr. 1, 73087, Bad Boll/Eckwälden, Germany
Keywords: Ethnopharmacological relevance: Mistletoe has been used since ancient times in Europe mostly for medicinal
Mistletoe purposes. Since 1917, mistletoe preparations have been applied in cancer therapy and today are the most fre-
Lectin quently used complementary medicine in tumor treatment. The main cytotoxic constituents of Viscum album are
Ricin lectins and viscotoxins.
Aim of the study: The aim of this in vitro study was to investigate the antiproliferative potential of Viscum album
preparations from diﬀerent host trees and to assess the impact of mistletoe lectin 1 (ML-1) and viscotoxin A (VT-
A) in comparison to a structurally similar lectin and thionin.
Materials and methods: By means of widely accepted 2D Alamar Blue Assay, based on population counting of
living FSL-1 using a fluorescent cell viability dye, the potential impact to inhibit tumor cell of the mistletoe
preparations (Iscucin®) and their single compounds (ML-1 and VT-A) on the cell growth of six human cancer cell
lines were evaluated. Also the mixture of ML-1 and VT-A corresponding to the contents in the specific mistletoe
preparations were monitored. Ricin and purothionin were used as reference lectin and reference thionin, re-
Results: The lung carcinoma cell line HCC827 was very sensitive to the Iscucin® preparations. Very strong an-
tiproliferative eﬀects were found with Iscucin® Salicis and Tiliae and a strong with Iscucin® Crataegi, Mali and
Populi. The IC50 concentrations of the Iscucin® preparations correlated with their respective ML-1 contents, but
much more eﬀective than ricin. Iscucin® preparations, ML-1 and ricin showed antiproliferative activity on human
tumor cells. VT-A and purothionin had no eﬀect on cell viability in the concentration ranges tested.
Conclusion: The complete mistletoe extract is more potent to inhibit tumor cell proliferation than isolated ML-1
at an equivalent concentration level. Phenolic compounds found in all Iscucin® preparations might contribute to
uphold the cytotoxic activity of ML-1 by antioxidative action. However, further studies are necessary to evaluate
the role of VT-A and possible synergistic actions to the antiproliferative eﬀect of aqueous mistletoe extracts.
Viscum album L. is taxonomically grouped with the Santalaceae. It grows as evergreen hemiparasite sphere on deciduous trees, except on beechs and on yews, but also on firs and pines. Mistletoe has smooth and oval leaves that are arranged in pairs. In February and March little inconspicuous yellow-green duds appear. In late autumn or early winter white and waxy berries mature. The seeds in the berries are coated with a sticky material called viscin (Urech and Ramm, 1997). There are two
green embryos in the seed, each producing its hypocotyl and then in-vading the wood by the haustorium (Ramm, 2000; Urech and Ramm, 1997). Approximately one third of the carbohydrates and amino acids come from the host tree, as well as highly specific ingredients such as salicin or caﬀeic acid from the willow bark (Gärtner et al., 2015, 2016; Felenda and Stintzing, 2017; Kunz, 2008). With respect to pharmaco-logically relevant ingredients, two compounds are in the forefront, mistletoe lectin (ML) and viscotoxin (VT) (Urech and Ramm, 1997; Urech et al., 2004). The contents depend on time of harvest, the year of harvest, edaphic conditions, the respective host tree and on the col-lected plant parts (Rippe, 2010). ML is found in particular in the stems