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Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Review Article

Biotechnology of Viscum Album L. and Cancer Treatment: A Review

Author(s): Vasileios Tsekouras* and Spyridon Kintzios

Volume 16, Issue 6, 2020

Page: [738 - 746] Pages: 9

DOI: 10.2174/1573407215666190410151958

Price: $65

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Abstract

Background: This review aims to highlight biotechnological techniques applied for the identification, isolation and propagation of mistletoe-derived bioactive compounds and the preclinical evaluation of their anticancer properties.

Methods: We undertook a structured search of bibliographic databases to identify and evaluate the literature, regarding biotechnology of mistletoe and malignancy treatment. The selected articles were classified into five modules according to the study design.

Results: Firstly, we have provided an overview of the role of biotechnology in plant-derived pharmaceuticals, by reviewing twelve articles. Then, V. album L. botany and a retrospection of the plant pharmaceutical applications are presented from a set of ten articles. Subsequently, mistletoe derived compounds and their anticancer properties are highlighted, throughout sixty-two articles, which emphasized the mechanisms of antitumor action. The next module is referred to as the biosynthesis of mistletoe bioactive compounds, covering nine cases of ‘in vitro’ propagation and genetic manipulation. Finally, fourteen assays regarding mistletoe preparations and preclinical testing for chemosensitivity are presented.

Conclusion: Biotechnology provides essential tools for the identification, production and evaluation of anticancer compounds derived from Viscum album L. The preclinical studies indicate the potential use of V. album preparations in chemotherapy but further research is essential for standardizing the therapeutic benefits of mistletoe compounds in the treatment of malignancies.

Keywords: Mistletoe, biotechnology, extracts, lectins, in vitro, in vivo, chemotherapy.

Graphical Abstract

[1]
Sharfstein, S.T. Biotechnology. Reference Module in Life Sciences; Elsevier: Amsterdam, Netherlands, 2017.
[http://dx.doi.org/10.1016/B978-0-12-809633-8.12382-9]
[2]
Deeni, Y.; Beccari, T.; Dundar, M.; Gartland, S.J.; Maffia, M. ViolaMagni, M.; Gartland, M.A.K. Novel technologies and their applications in biotechnology. European J. Biotechnol. Biosci., 2014, 2(6), 13-19.
[3]
Ghorbani, M.; Karimi, H. Role of biotechnology in cancer control. IJSRST, 2015, 1(5), 180-185.
[4]
Veeresham, C. Natural products derived from plants as a source of drugs. J. Adv. Pharm. Technol. Res., 2012, 3(4), 200-201.
[http://dx.doi.org/10.4103/2231-4040.104709] [PMID: 23378939]
[5]
Shen, B. A new golden age of natural products drug discovery. Cell, 2015, 163(6), 1297-1300.
[http://dx.doi.org/10.1016/j.cell.2015.11.031] [PMID: 26638061]
[6]
Khan, M.Y.; Aliabbas, S.; Kumar, V.; Rajkumar, S. Recent advances in medicinal plant biotechnology. Indian J. Biotechnol., 2009, 8, 9-22.
[7]
Demain, A.L.; Vaishnav, P. Natural products for cancer chemotherapy. Microb. Biotechnol., 2011, 4(6), 687-699.
[http://dx.doi.org/10.1111/j.1751-7915.2010.00221.x] [PMID: 21375717]
[8]
Greenwell, M.; Rahman, P.K.S.M. Medicinal plants: Their use in anticancer treatment. Int. J. Pharm. Sci. Res., 2015, 6(10), 4103-4112.
[PMID: 26594645]
[9]
Atanasov, A.G.; Waltenberger, B.; Pferschy-Wenzig, E.M.; Linder, T.; Wawrosch, C.; Uhrin, P.; Temml, V.; Wang, L.; Schwaiger, S.; Heiss, E.H.; Rollinger, J.M.; Schuster, D.; Breuss, J.M.; Bochkov, V.; Mihovilovic, M.D.; Kopp, B.; Bauer, R.; Dirsch, V.M.; Stuppner, H. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol. Adv., 2015, 33(8), 1582-1614.
[http://dx.doi.org/10.1016/j.biotechadv.2015.08.001] [PMID: 26281720]
[10]
Mollica, A.; Stefanucci, A.; Feliciani, F.; Cacciatore, I.; Cornacchia, C.; Pinnen, F. Delivery methods of camptothecin and its hydrosoluble analogue irinotecan for treatment of colorectal cancer. Curr. Drug Deliv., 2012, 9(2), 122-131.
[http://dx.doi.org/10.2174/156720112800234558] [PMID: 22283650]
[11]
Mollica, A.; Costante, R.; Fiorito, S.; Genovese, S.; Stefanucci, A.; Mathieu, V.; Kiss, R.; Epifano, F. Synthesis and anti-cancer activity of naturally occurring 2,5-diketopiperazines. Fitoterapia, 2014, 98, 91-97.
[http://dx.doi.org/10.1016/j.fitote.2014.07.010] [PMID: 25064216]
[12]
Khan, A.; Waqar, K.; Shafique, A.; Irfan, R.; Gul, A. The engineering towards understanding human diseases and therapeutic interventions. Omics Technologies and Bio-Engineering; Barh, D; Azevedo, V., Ed.; Academic Press, 2018, pp. 431-448.
[http://dx.doi.org/10.1016/B978-0-12-804659-3.00018-X]
[13]
Neagu, M.; Albulescu, R.; Tanase, C. Biotechnology landscape in cancer drug discovery. Future Sci. OA, 2015, 1(3), FSO12.
[http://dx.doi.org/10.4155/fso.15.10] [PMID: 28031887]
[14]
Zips, D.; Thames, H.D.; Baumann, M. New anticancer agents: In Vitro and in vivo evaluation. In Vivo, 2005, 19(1), 1-7.
[PMID: 15796152]
[15]
Fukunaga, T.; Kajikawa, I.; Nishiya, K.; Watanabe, Y.; Takeya, K.; Itokawa, H. Studies on the constituents of the European Mistletoe, Viscum album L. Chem. Pharm. Bull. (Tokyo), 1987, 35, 3292-3297.
[http://dx.doi.org/10.1248/cpb.35.3292]
[16]
Zuber, D. Biological flora of Central Europe: Viscum album L. Flora, 2004, 199(3), 181-203.
[http://dx.doi.org/10.1078/0367-2530-00147]
[17]
Becker, H. Botany of European mistletoe (Viscum album L.). Oncology, 1986, 43(1)(Suppl. 1), 2-7.
[http://dx.doi.org/10.1159/000226413] [PMID: 3808574]
[18]
Podlech, O.; Harter, P.N.; Mittelbronn, M.; Pöschel, S.; Naumann, U. Fermented mistletoe extract as a multimodal antitumoral agent in gliomas. Evid. Based Complement. Alternat. Med., 2012.2012501796
[http://dx.doi.org/10.1155/2012/501796] [PMID: 23133496]
[19]
Schink, M.; Dehus, O. Effects of mistletoe products on pharmacokinetic drug turnover by inhibition and induction of cytochrome P450 activities. BMC Complement. Altern. Med., 2017, 17(1), 521.
[http://dx.doi.org/10.1186/s12906-017-2028-1] [PMID: 29202738]
[20]
Paine, K.L.; Harrison, C.H. Mistletoe: Its role in horticulture and human life. Horttechnology, 1992, 2(3), 324-330.
[http://dx.doi.org/10.21273/HORTTECH.2.3.324]
[21]
Bar-Sela, G. White-Berry Mistletoe (Viscum album L.) as complementary treatment in cancer: Does it help? Eur. J. Integr. Med., 2011, 3(2), e55-e62.
[http://dx.doi.org/10.1016/j.eujim.2011.03.002]
[22]
Steele, M.L.; Axtner, J.; Happe, A.; Kröz, M.; Matthes, H.; Schad, F. Safety of intravenous application of Mistletoe (Viscum album L.) Preparations in oncology: An observational study. Evid. Based Complement. Alternat. Med., 2014, 2014, 236310.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052504/
[23]
Sunjic, S.B.; Gasparovic, A.C.; Vukovic, T.; Weiss, T.; Weiss, E.S.; Soldo, I.; Djakovic, N.; Zarkovic, T.; Zarkovic, N. Adjuvant cancer biotherapy by Viscum album extract Isorel: Overview of evidence based medicine findings. Coll. Antropol., 2015, 39(3), 701-708.
[PMID: 26898069]
[24]
Wrotek, S.; Skawiński, R.; Kozak, W. Immunostimulatory properties of mistletoe extracts and their application in oncology. Postepy Hig. Med. Dosw., 2014, 68, 1216-1224.
[http://dx.doi.org/10.5604/17322693.1126850] [PMID: 25380204]
[25]
Schumacher, U.; Adam, E.; Kretzschmar, H.; Pfüller, U. Binding patterns of mistletoe lectins I, II and III to microglia and Alzheimer plaque glycoproteins in human brains. Acta Histochem., 1994, 96(4), 399-403.
[http://dx.doi.org/10.1016/S0065-1281(11)80025-5] [PMID: 7717044]
[26]
Konopa, J.; Woynarowski, J.M.; Lewandowska-Gumieniak, M. Isolation of viscotoxins. Cytotoxic basic polypeptides from Viscum album L. Hoppe Seylers Z. Physiol. Chem., 1980, 361(10), 1525-1533.
[http://dx.doi.org/10.1515/bchm2.1980.361.2.1525] [PMID: 7450674]
[27]
Kang, S-N. Ethanol extracts from Mistletoe (Viscum album L.) act as natural antioxidants and antimicrobial agents in uncooked pork patties during refrigerated storage. Asian-Australas. J. Anim. Sci., 2016, 29(1), 109-118.
[http://dx.doi.org/10.5713/ajas.15.0253] [PMID: 26732334]
[28]
Deliorman, O.D.; Calis, I.; Ergun, F. Two new flavonoid glycosides from Viscum album ssp. album. Pharm. Biol., 2002, 40(5), 380-383.
[http://dx.doi.org/10.1076/phbi.40.5.380.8460]
[29]
Wójciak-Kosior, M.; Sowa, I.; Pucek, K.; Szymczak, G.; Kocjan, R.; Luchowski, P. Evaluation of seasonal changes of triterpenic acid contents in Viscum album from different host trees. Pharm. Biol., 2017, 55(1), 1-4.
[http://dx.doi.org/10.1080/13880209.2016.1225773] [PMID: 27593449]
[30]
Kleinsimon, S.; Kauczor, G.; Jaeger, S.; Eggert, A.; Seifert, G.; Delebinski, C. ViscumTT induces apoptosis and alters IAP expression in osteosarcoma in vitro and has synergistic action when combined with different chemotherapeutic drugs. BMC Complement. Altern. Med., 2017, 17(1), 26.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219806/
[http://dx.doi.org/10.1186/s12906-016-1545-7] [PMID: 28061770]
[31]
Amer, B.; Juvik, J.O.; Dupont, F.; Francis, W.G.; Fossen, T. Novel aminoalkaloids from European mistletoe (Viscum al-bum L.). Phytochem. Lett., 2012, 5(3), 677-681.
[http://dx.doi.org/10.1016/j.phytol.2012.07.005]
[32]
Mueller, E.A.; Anderer, F.A. Chemical specificity of effector cell/tumor cell bridging by a Viscum album rhamnogalacturonan enhancing cytotoxicity of human NK cells. Immunopharmacology, 1990, 19(1), 69-77.
[http://dx.doi.org/10.1016/0162-3109(90)90028-D] [PMID: 2407685]
[33]
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(1A), 23-28.
[PMID: 10226520]
[34]
Nazaruk, J.; Orlikowski, P. Phytochemical profile and therapeutic potential of Viscum album L. Nat. Prod. Res., 2016, 30(4), 373-385.
[http://dx.doi.org/10.1080/14786419.2015.1022776] [PMID: 25813519]
[35]
Urech, K.; Baumgartner, S. Chemical constituents of Viscum album L.: Implications for the pharmaceutical preparation of mistletoe. Transl Res Biomed., 2015, 4, 11-23.
[36]
Peumans, W.J.; Verhaert, P.; Pfüller, U.; Van Damme, E.J.M. Isolation and partial characterization of a small chitin-binding lectin from mistletoe (Viscum album). FEBS Lett., 1996, 396(2-3), 261-265.
[http://dx.doi.org/10.1016/0014-5793(96)01108-8] [PMID: 8914999]
[37]
Schaller, G.; Urech, K.; Grazi, G.; Giannattasio, M. Viscotoxin composition of the three European subspecies of Viscum album. Planta Med., 1998, 64(7), 677-678.
[http://dx.doi.org/10.1055/s-2006-957553] [PMID: 17253311]
[38]
Vicas, S.; Rugina, D.; Leopold, L.; Pintea, A.; Socaciu, C. Fingerprint of bioactive compounds and antioxidant activities of Viscum album from different host trees. Not. Bot. Horti Agrobot. Cluj-Napoca, 2011, 39(1), 48-57.
[http://dx.doi.org/10.15835/nbha3913455]
[39]
Voelter, W.; Wacker, R.; Stoeva, S.; Tsitsilonis, R.; Betzel, C. Mistletoe lectins, structure and function. Front. Nat. Pro. Chem., 2005, 1(1), 149-162.
[http://dx.doi.org/10.2174/1574089054583597]
[40]
Lavelle, E.C.; Grant, G.; Pusztai, A.; Pfüller, U.; Leavy, O.; McNeela, E.; Mills, K.H.; O’Hagan, D.T. Mistletoe lectins enhance immune responses to intranasally co-administered herpes simplex virus glycoprotein D2. Immunology, 2002, 107(2), 268-274.
[http://dx.doi.org/10.1046/j.1365-2567.2002.01492.x] [PMID: 12383207]
[41]
Franz, H.; Ziska, P.; Kindt, A. Isolation and properties of three lectins from mistletoe (Viscum album L.). Biochem. J., 1981, 195(2), 481-484.
[http://dx.doi.org/10.1042/bj1950481] [PMID: 7316963]
[42]
Endo, Y.; Mitsui, K.; Motizuki, M.; Tsurugi, K. The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28 S ribosomal RNA caused by the toxins. J. Biol. Chem., 1987, 262(12), 5908-5912.
[PMID: 3571242]
[43]
Schrot, J.; Weng, A.; Melzig, M.F. Ribosome-inactivating and related proteins. Toxins (Basel), 2015, 7(5), 1556-1615.
[http://dx.doi.org/10.3390/toxins7051556] [PMID: 26008228]
[44]
Zarkovic, N.; Vukovic, T.; Loncaric, I.; Miletic, M.; Zarkovic, K.; Borovic, S.; Cipak, A.; Sabolovic, S.; Konitzer, M.; Mang, S. An overview on anticancer activities of the Viscum album extract Isorel. Cancer Biother. Radiopharm., 2001, 16(1), 55-62.
[http://dx.doi.org/10.1089/108497801750096041] [PMID: 11279798]
[45]
Kunze, E.; Schulz, H.; Ahrens, H.; Gabius, H.J. Lack of an antitumoral effect of immunomodulatory galactoside-specific mistletoe lectin on N-methyl-N-nitrosourea-induced urinary bladder carcinogenesis in rats. Exp. Toxicol. Pathol., 1997, 49(3-4), 167-180.
[http://dx.doi.org/10.1016/S0940-2993(97)80004-8] [PMID: 9314050]
[46]
Thies, A.; Dautel, P.; Meyer, A.; Pfüller, U.; Schumacher, U. Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model. Br. J. Cancer, 2008, 98(1), 106-112.
[http://dx.doi.org/10.1038/sj.bjc.6604106] [PMID: 18026191]
[47]
Zarković, N.; Kalisnik, T.; Loncarić, I.; Borović, S.; Mang, S.; Kissel, D.; Konitzer, M.; Jurin, M.; Grainza, S. 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. Cancer Biother. Radiopharm., 1998, 13(2), 121-131.
[http://dx.doi.org/10.1089/cbr.1998.13.121] [PMID: 10850348]
[48]
Marvibaigi, M.; Supriyanto, E.; Amini, N. Abdul, Majid, F.A.; Jaganathan, S.K. Preclinical and clinical effects of mistletoe against breast cancer. BioMed Res. Int., 2014, 2014, 785479.
[http://dx.doi.org/10.1155/2014/785479] [PMID: 25136622]
[49]
Fritz, P.; Dippon, J.; Kierschke, T.; Siegle, I.; Möhring, A.; Moisa, A.; Mürdter, T.E. Impact of mistletoe lectin binding in breast cancer. Anticancer Res., 2004, 24(2C), 1187-1192.
[PMID: 15154645]
[50]
Burger, A.M.; Mengs, U.; Schüler, J.B.; Fiebig, H.H. Antiproliferative activity of an aqueous mistletoe extract in human tumor cell lines and xenografts in vitro. Arzneimittelforschung, 2001, 51(9), 748-757.
[PMID: 11642008]
[51]
Vervecken, W.; Kleff, S.; Pfüller, U.; Büssing, A. Induction of apoptosis by mistletoe lectin I and its subunits. No evidence for cytotoxic effects caused by isolated A- and B-chains. Int. J. Biochem. Cell Biol., 2000, 32(3), 317-326.
[http://dx.doi.org/10.1016/S1357-2725(99)00135-1] [PMID: 10716629]
[52]
Rostock, M.; Huber, R.; Greiner, T.; Fritz, P.; Scheer, R.; Schueler, J.; Fiebig, H.H. Anticancer activity of a lectin-rich mistletoe extract injected intratumorally into human pancreatic cancer xenografts. Anticancer Res., 2005, 25(3B), 1969-1975.
[PMID: 16158932]
[53]
Steinborn, C.; Klemd, A.M.; Sanchez-Campillo, A.S.; Rieger, S.; Scheffen, M.; Sauer, B.; Garcia-Käufer, M.; Urech, K.; Follo, M.; Ücker, A.; Kienle, G.S.; Huber, R.; Gründemann, C. Viscum album neutralizes tumor-induced immunosuppression in a human in vitro cell model. PLoS One,, 2017, 12(7), e0181553.https://www.ncbi.nlm.nih.gov/pubmed/28719632
[http://dx.doi.org/10.1371/journal.pone.0181553] [PMID: 28719632]
[54]
Antony, S.; Kuttan, R.; Kuttan, G. Effect of Viscum album in the inhibition of lung metastasis in mice induced by B16F10 melanoma cells. J. Exp. Clin. Cancer Res., 1997, 16(2), 159-162.
[PMID: 9261741]
[55]
Valentiner, U.; Pfüller, U.; Baum, C.; Schumacher, U. The cytotoxic effect of mistletoe lectins I, II and III on sensitive and multidrug resistant human colon cancer cell lines in vitro. Toxicology, 2002, 171(2-3), 187-199.
[http://dx.doi.org/10.1016/S0300-483X(01)00581-9] [PMID: 11836024]
[56]
von Schoen-Angerer, T.; Goyert, A.; Vagedes, J.; Kiene, H.; Merckens, H.; Kienle, G.S. Disappearance of an advanced adenomatous colon polyp after intratumoural injection with Viscum album (European mistletoe) extract: A case report. J. Gastrointestin. Liver Dis., 2014, 23(4), 449-452.
[http://dx.doi.org/10.15403/jgld.2014.1121.234.acpy] [PMID: 25532007]
[57]
Onay-Uçar, E.; Erol, O.; Kandemir, B.; Mertoğlu, E.; Karagöz, A.; Arda, N. Viscum album L. extracts protects HeLa cells against nuclear and mitochondrial DNA damage. Evid. Based Complement. Alternat. Med., 2012., 2012958740. https://www.ncbi.nlm.nih.gov/pubmed/22988477
[http://dx.doi.org/10.1155/2012/958740] [PMID: 22988477]
[58]
Bussing, A. Induction of apoptosis by the mistletoe lectins: A review on the mechanisms of cytotoxicity mediated by Viscum album L. Apoptosis, 1996, 1, 25-32.
[http://dx.doi.org/10.1007/BF00142075]
[59]
Bantel, H.; Engels, I.H.; Voelter, W.; Schulze-Osthoff, K.; Wesselborg, S. Mistletoe lectin activates caspase-8/FLICE independently of death receptor signaling and enhances anticancer drug-induced apoptosis. Cancer Res., 1999, 59(9), 2083-2090.
[PMID: 10232592]
[60]
Kirsch, A.; Hajto, T. Case reports of sarcoma patients with optimized lectin-oriented mistletoe extract therapy. J. Altern. Complement. Med., 2011, 17(10), 973-979.https://www.ncbi.nlm.nih.gov/pubmed/22010781
[http://dx.doi.org/10.1089/acm.2010.0596] [PMID: 22010781]
[61]
Hajto, T.; Hostanska, K.; Fischer, J.; Saller, R. Immunomodulatory effects of Viscum album agglutinin-I on natural immunity. Anticancer Drugs, 1997, 8(1)(Suppl. 1), S43-S46.
[http://dx.doi.org/10.1097/00001813-199704001-00010] [PMID: 9179367]
[62]
Klein, R.; Classen, K.; Berg, P.A.; Lüdtke, R.; Werner, M.; Huber, R. In vivo-induction of antibodies to mistletoe lectin-1 and viscotoxin by exposure to aqueous mistletoe extracts: A randomised double-blinded placebo controlled phase I study in healthy individuals. Eur. J. Med. Res., 2002, 7(4), 155-163.
[PMID: 12010650]
[63]
Braun, J.M.; Ko, H.L.; Schierholz, J.M.; Weir, D.; Blackwell, C.C.; Beuth, J. Application of standardized mistletoe extracts augment immune response and down regulates metastatic organ colonization in murine models. Cancer Lett., 2001, 170(1), 25-31.
[http://dx.doi.org/10.1016/S0304-3835(01)00517-1] [PMID: 11448531]
[64]
Heiny, B.M.; Beuth, J. Mistletoe extract standardized for the galactoside-specific lectin (ML-1) induces beta-endorphin release and immunopotentiation in breast cancer patients. Anticancer Res., 1994, 14(3B), 1339-1342.
[PMID: 8067703]
[65]
Florack, D.E.; Stiekema, W.J. Thionins: properties, possible biological roles and mechanisms of action. Plant Mol. Biol., 1994, 26(1), 25-37.
[http://dx.doi.org/10.1007/BF00039517] [PMID: 7948874]
[66]
Urech, K.; Schaller, G.; Jäggy, C. Viscotoxins, mistletoe lectins and their isoforms in mistletoe (Viscum album L.) extracts Iscador. Arzneimittelforschung, 2006, 56(6A), 428-434.
[PMID: 16927522]
[67]
Bogomolovas, J.; Simon, B.; Sattler, M.; Stier, G. Screening of fusion partners for high yield expression and purification of bioactive viscotoxins. Protein Expr. Purif., 2009, 64(1), 16-23.
[http://dx.doi.org/10.1016/j.pep.2008.10.003]
[68]
Schaller, G.; Urech, K.; Giannattasio, M. Cytotoxicity of different viscotoxins and extracts from the european subspecies of Viscum album L. Phytother. Res., 1996, 1996(10), 473-477.
[http://dx.doi.org/10.1002/(SICI)1099-1573(199609)10:6<473::AID-PTR879>3.0.CO;2-Q]
[69]
Knöpfl-Sidler, F.; Viviani, A.; Rist, L.; Hensel, A. Human cancer cells exhibit in vitro individual receptiveness towards different mistletoe extracts. Pharmazie, 2005, 60(6), 448-454.
[PMID: 15997835]
[70]
Wagner, H.; Jordan, E.; Zänker, K.S. Cell-mediated and direct cytotoxicity of purified ingredients of Viscum album. J. Cancer Res. Clin. Oncol., 1987, 1987, 53.
[71]
Tabiasco, J.; Pont, F.; Fournié, J.J.; Vercellone, A. Mistletoe viscotoxins increase natural killer cell-mediated cytotoxicity. Eur. J. Biochem., 2002, 269(10), 2591-2600.
[http://dx.doi.org/10.1046/j.1432-1033.2002.02932.x] [PMID: 12027898]
[72]
Klein, R.; Classen, K.; Fischer, S.; Errenst, M.; Scheffler, A.; Stein, G.M.; Scheer, R.; von Laue, H.B. Induction of antibodies to viscotoxins A1, A2, A3, and B in tumor patients during therapy with an aqueous mistletoe extract. Eur. J. Med. Res., 2002, 7(8), 359-367.
[PMID: 12204844]
[73]
Stein, G.M.; Schaller, G.; Pfüller, U.; Schietzel, M.; Büssing, A. Thionins from Viscum album L: Influence of the viscotoxins on the activation of granulocytes. Anticancer Res., 1999, 19(2A), 1037-1042.
[PMID: 10368652]
[74]
Kuttan, G.; Vasudevan, D.M.; Kuttan, R. Isolation and identification of a tumour reducing component from mistletoe extract (Iscador). Cancer Lett., 1988, 41(3), 307-314.
[http://dx.doi.org/10.1016/0304-3835(88)90292-3] [PMID: 3409209]
[75]
Kuttan, G.; Kuttan, R. Immunological mechanism of action of the tumor reducing peptide from mistletoe extract (NSC 635089) cellular proliferation. Cancer Lett., 1992, 66(2), 123-130.
[http://dx.doi.org/10.1016/0304-3835(92)90224-J] [PMID: 1394116]
[76]
Oldfield, E.; Lin, F.Y. Terpene Biosynthesis: Modularity rules. Angew. Chem. Int. Ed. Engl., 2011, 51(5), 1124-1137.
[77]
Patlolla, J.M.; Rao, C.V. Triterpenoids for cancer prevention and treatment: Current status and future prospects. Curr. Pharm. Biotechnol., 2012, 13(1), 147-155.
[http://dx.doi.org/10.2174/138920112798868719] [PMID: 21466427]
[78]
Huang, M.; Lu, J.J.; Huang, M.Q.; Bao, J.L.; Chen, X.P.; Wang, Y.T. Terpenoids: Natural products for cancer therapy. Expert Opin. Investig. Drugs, 2012, 21(12), 1801-1818.
[http://dx.doi.org/10.1517/13543784.2012.727395] [PMID: 23092199]
[79]
Urech, K.; Scher, J.M.; Hostanska, K.; Becker, H. Apoptosis inducing activity of viscin, a lipophilic extract from Viscum album L. J. Pharm. Pharmacol., 2005, 57(1), 101-109.
[http://dx.doi.org/10.1211/0022357055083] [PMID: 15638998]
[80]
Delebinski, C.I.; Jäger, S.; Kemnitz-Hassanin, K.; Henze, G.; Lode, H.N.; Seifert, G. Therapeutic efficacy of natural compounds from Viscum album L. in acute lymphoblastic leukaemia. Blood, 2010, 116(21), 3261.
[http://dx.doi.org/10.1182/blood.V116.21.3261.3261]
[81]
Delebinski, C.I.; Twardziok, M.; Kleinsimon, S.; Hoff, F.; Mulsow, K.; Rolff, J.; Jäger, S.; Eggert, A.; Seifert, G. A Natural Combination Extract of Viscum album L. Containing Both triterpene acids and lectins is highly effective against AML in vivo. PLoS One, 2015, 10(8)e0133892https://www.ncbi. nlm.nih.gov/pubmed/26244918
[http://dx.doi.org/10.1371/journal.pone.0133892] [PMID: 26244918]
[82]
Twardziok, M.; Kleinsimon, S.; Rolff, J.; Jäger, S.; Eggert, A.; Seifert, G.; Delebinski, C.I. Multiple active compounds from Viscum album L. Synergistically converge to promote apoptosis in Ewing sarcoma. PLoS One, 2016, 11(9)e0159749https://www.ncbi.nlm.nih.gov/pubmed/27589063
[http://dx.doi.org/10.1371/journal.pone.0159749] [PMID: 27589063]
[83]
Strüh, C.M.; Jäger, S.; Schempp, C.M.; Scheffler, A.; Martin, S.F. A novel triterpene extract from mistletoe induces rapid apoptosis in murine B16.F10 melanoma cells. Phytother. Res., 2012, 26(10), 1507-1512.
[http://dx.doi.org/10.1002/ptr.4604] [PMID: 22318938]
[84]
Delebinski, C.I.; Jaeger, S.; Kemnitz-Hassanin, K.; Henze, G.; Lode, H.N.; Seifert, G.J. A new development of triterpene acid-containing extracts from Viscum album L. displays synergistic induction of apoptosis in acute lymphoblastic leukaemia. Cell Prolif., 2012, 45(2), 176-187.
[http://dx.doi.org/10.1111/j.1365-2184.2011.00801.x] [PMID: 22221251]
[85]
Stammer, R.M.; Kleinsimon, S.; Rolff, J.; Jäger, S.; Eggert, A.; Seifert, G.; Delebinski, C.I. Synergistic antitumour properties of viscumTT in alveolar rhabdomyosarcoma. J. Immunol. Res., 2017. 20174874280 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534308/
[http://dx.doi.org/10.1155/2017/4874280] [PMID: 28791312 ]
[86]
Mulsow, K.; Enzlein, T.; Delebinski, C.; Jaeger, S.; Seifert, G.; Melzig, M.F. Impact of mistletoe triterpene acids on the uptake of mistle-toe lectin by cultured tumor cells. PLoS One, 2016, 11(4) e0153825 https://www.ncbi.nlm.nih.gov/pubmed/
[87]
Twardziok, M.; Meierhofer, D.; Börno, S.; Timmermann, B.; Jäger, S.; Boral, S.; Eggert, A.; Delebinski, C.I.; Seifert, G. Transcriptomic and proteomic insight into the effects of a defined European mistletoe extract in Ewing sarcoma cells reveals cellular stress responses. BMC Complement. Altern. Med., 2017, 17(1), 237.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410041/
[http://dx.doi.org/10.1186/s12906-017-1715-2] [PMID: 28454538]
[88]
Estko, M.; Baumgartner, S.; Urech, K.; Kunz, M.; Regueiro, U.; Heusser, P.; Weissenstein, U. Tumour cell derived effects on monocyte/macrophage polarization and function and modulatory potential of Viscum album lipophilic extract in vitro. BMC Complement. Altern. Med., 2015, 15, 130.https://www.ncbi.nlm.nih. gov/pubmed/25902944
[http://dx.doi.org/10.1186/s12906-015-0650-3] [PMID: 25902944]
[89]
Khwaja, T.A.; Dias, C.B.; Pentecost, S. Recent studies on the anticancer activities of mistletoe (Viscum album) and its alkaloids. Oncology, 1986, 43(1)(Suppl. 1), 42-50.
[http://dx.doi.org/10.1159/000226419] [PMID: 3543783]
[90]
Melo, M.N.O.; Oliveira, A.P.; Wiecikowski, A.F.; Carvalho, R.S.; Castro, J.L.; de Oliveira, F.A.G.; Pereira, H.M.G.; da Veiga, V.F.; Capella, M.M.A.; Rocha, L.; Holandino, C. Phenolic compounds from Viscum album tinctures enhanced antitumor activity in melanoma murine cancer cells. Saudi Pharm. J., 2018, 26(3), 311-322.
[http://dx.doi.org/10.1016/j.jsps.2018.01.011] [PMID: 29556122]
[91]
Klett, C.Y.; Anderer, F.A. Activation of natural killer cell cytotoxicity of human blood monocytes by a low molecular weight component from Viscum album extract. Arzneimittelforschung, 1989, 39(12), 1580-1585.
[PMID: 2624609]
[92]
Becker, H.; Schwarz, G. Callus cultures from Viscum album. A possible source of raw materials for gaining therapeutic interesting extracts. Planta Med., 1971, 20(4), 357-362.
[http://dx.doi.org/10.1055/s-0028-1099716] [PMID: 5137754]
[93]
Ulrich, I.; Ulrich, W. Flow cytometric DNA analysis of plant protoplasts with DAPI. Zeitschrift fur Naturforschung, 1986, 41, 1052-1056.
[http://dx.doi.org/10.1515/znc-1986-11-1217]
[94]
Fukui, M.; Azuma, J.; Okamura, K. Induction of callus from mistletoe [Viscum album] and interaction with its host cells. Bulletin of the Kyoto University Forests, 1990, 62, 261-269.
[95]
Kintzios, S.; Barberaki, M. The Biotechnology of Viscum album L.: Tissue Culture, Somatic Embryogenesis and Proto-plast Isolation. Medicinal and Aromatic Plants-Industrial Approaches: The genus Viscum; Bussing, A., Ed.; Harwood Publishers: Amsterdam, 2000, pp. 95-100.
[96]
Kintzios, S.; Barberaki, M.; Tourgielis, P.; Aivalakis, G.; Voli-oti, A. Preliminary evaluation of somaclonal variation for the in vitro production of new toxic proteins from Viscum album L. J. Herbs Spices Med. Plants, 2002, 9(2-3), 217-221.
[http://dx.doi.org/10.1300/J044v09n02_31]
[97]
Barberaki, M.; Dermitzaki, E.; Margioris, N.A.; Theodosaki, M.; Grafakos, S.; Kintzios, S. Protein extracts from Somaclonal mistletoe (Viscum album L.) callus with increased tumor cytotoxic activity in vitro. Curr. Bioact. Compd., 2015, 11(2), 104-108.
[http://dx.doi.org/10.2174/1573407211666150602215615]
[98]
Eck, J.; Langer, M.; Möckel, B.; Baur, A.; Rothe, M.; Zinke, H.; Lentzen, H. Cloning of the mistletoe lectin gene and characterization of the recombinant A-chain. Eur. J. Biochem., 1999, 264(3), 775-784.
[http://dx.doi.org/10.1046/j.1432-1327.1999.00638.x] [PMID: 10491123]
[99]
Kourmanova, A.G.; Soudarkina, O.J.; Olsnes, S.; Kozlov, J.V. Cloning and characterization of the genes encoding toxic lectins in mistletoe (Viscum album L). Eur. J. Biochem., 2004, 271(12), 2350-2360.
[http://dx.doi.org/10.1111/j.1432-1033.2004.04153.x] [PMID: 15182350]
[100]
Tonevitsky, A.G.; Agapov, I.I.; Pevzner, I.B.; Maluchenko, N.V.; Moisenovich, M.M.; Palmer, R.A.; Yurkova, M.; Pfüller, K.; Pfüller, U. A new gene encoding the ribosome-inactivating protein from mistletoe extracts. Arzneimittelforschung, 2004, 54(4), 242-249.
[PMID: 15146937]
[101]
Giacometti, J. Plant lectins in cancer prevention and treatment. Medicina Fluminensis, 2015, 51(2), 211-229.
[102]
Klingbeil, M.F.; Xavier, F.C.; Sardinha, L.R.; Severino, P.; Mathor, M.B.; Rodrigues, R.V.; Pinto, D.S. Jr Cytotoxic effects of mistletoe (Viscum album L.) in head and neck squamous cell carcinoma cell lines. Oncol. Rep., 2013, 30(5), 2316-2322.https://www.ncbi.nlm.nih.gov/pubmed/24026291
[http://dx.doi.org/10.3892/or.2013.2732] [PMID: 24026291]
[103]
Baumgartner, S.; Flückiger, H.; Kunz, M.; Scherr, C.; Urech, K. Evaluation of preclinical assays to investigate an anthroposophic pharmaceutical process applied to Mistletoe (Viscum album L.). Extracts. Evid. Based Complement. Alternat. Med., 2014, 2014620974
[http://dx.doi.org/10.1155/2014/620974] [PMID: 24876872]
[104]
Kelter, G.; Schierholz, J.M.; Fischer, I.U.; Fiebig, H.H. Cytotoxic activity and absence of tumor growth stimulation of standardized mistletoe extracts in human tumor models in vitro. Anticancer Res., 2007, 27(1A), 223-233.
[PMID: 17352237]
[105]
Weissenstein, U.; Kunz, M.; Urech, K.; Baumgartner, S. Interaction of standardized mistletoe (Viscum album) extracts with chemotherapeutic drugs regarding cytostatic and cytotoxic effects in vitro. BMC Complement. Altern. Med., 2014, 14, 6.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893555/
[http://dx.doi.org/10.1186/1472-6882-14-6] [PMID: 24397864]
[106]
Kim, S.; Kim, K.C.; Lee, C. Mistletoe (Viscum album) extract targets Axl to suppress cell proliferation and overcome cisplatin- and erlotinib-resistance in non-small cell lung cancer cells. Phytomedicine, 2017, 36, 183-193.
[http://dx.doi.org/10.1016/j.phymed.2017.09.017] [PMID: 29157814]
[107]
Burkhart, J.; Wälchli, C.; Heusser, P.; Weissenstein, U.; Baumgartner, S.; Andres, A.C. In vitro investigation into the potential of a mistletoe extract to alleviate adverse effects of cyclophosphamide. Altern. Ther. Health Med., 2010, 16(3), 40-48.
[PMID: 20486623]
[108]
Schötterl, S.; Huber, S.M.; Lentzen, H.; Mittelbronn, M.; Naumann, U. Adjuvant therapy using mistletoe containing drugs boosts the T Cell-Mediated killing of Glioma Cells and prolongs the survival of Glioma bearing mice. Evid. Based Complement. Alternat. Med., 2018, 2018 ,3928572
[http://dx.doi.org/10.1155/2018/3928572] [PMID: 30224928]
[109]
Seifert, G.; Jesse, P.; Laengler, A.; Reindl, T.; Lüth, M.; Lo-bitz, S.; Henze, G.; Prokop, A.; Lode, H.N. Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro. Cancer Lett., 2008, 264(2), 218-28.https://www.ncbi.nlm.nih.gov/pubmed/18314258
[110]
Weber, K.; Mengs, U.; Schwarz, T.; Hajto, T.; Hostanska, K.; Allen, T.R.; Weyhenmeyer, R.; Lentzen, H. Effects of a standardized mistletoe preparation on metastatic B16 melanoma colonization in murine lungs. Arzneimittelforschung, 1998, 48(5), 497-502.
[PMID: 9638318]

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