Mistletoe in cancer

Bioactive compounds found in mistletoe include lectins, flavonoids, viscotoxins, oligo-and polysaccharides, alkaloids, membrane lipids, and others (1). Of all these, lectins mediate several immunological activities with direct anti-cancer effects (2).

Major effects of mistletoe administration in cancer

Immunomodulatory effects

● increases the number of leukocytes, eosinophils and granulocytes and macrophages (3)
● increases cytokine production (4)
● increases the number of lymphocytes (5)
● increases the number of NK (natural killer) cells and their activity (6)
● increases the number of neutrophils and granulocytes (7)
● improves cellular and humoral immunity (8)
● increases the activity of NK immune cells during and after surgery (9)
● enhances dendritic cell maturation (10)
● blocks tumor immunosuppression against dendritic cells (11)

Anti-inflammatory action

Mistletoe treatment also proves useful in lowering COX-2 levels, which implies a reduction in procancerous inflammation (12)

Antitumor action

Additionally, studies show that mistletoe has cytotoxic (13), proapoptotic (14) and anti-tumor (15) effects. Down-regulation of PI3K/AKT and MAPK, which are responsible with tumor cell proliferation and survival, is one of the molecular mechanisms behind mistletoe's therapeutic value. By inhibiting AKT phosphorylation, cancer cells undergo apoptosis through down-regulation of BCL2, BCL2L1, MCL1, XIAP, and up-regulation of the proapoptotic protein Bax and cytochrome C.

Increasing the quality of life

The majority of studies show that mistletoe treatment significantly improves cancer patients' quality of life and lessens the side effects of chemotherapy and radiation therapy (16).  As a result, studies demonstrate improvements in patients' fatigue and exhaustion, ability to cope with the illness (17), sleep issues, nausea and appetite, depression and anxiety, job capacity, emotional and functional well-being, and so on (18). The most important effect of mistletoe is that it strengthens anti-tumor immunity.
  1. Oei, Shiao Li, Anja Thronicke, and Friedemann Schad. "Mistletoe and immunomodulation: insights and implications for anticancer therapies." Evidence-Based Complementary and Alternative Medicine 2019 (2019).
  2.  Huber, Roman, et al. "Mistletoe treatment induces GM-CSF-and IL-5 production by PBMC and increases blood granulocyte-and eosinophil counts: a placebo controlled randomized study in healthy subjects." European journal of medical research 10.10 (2005): 411.
  3. Huber, Roman, et al. "Safety and effects of two mistletoe preparations on production of Interleukin-6 and other immune parameters-a placebo controlled clinical trial in healthy subjects." BMC complementary and alternative medicine 11.1 (2011): 1-12.
  4.  Hajto, Tibor, et al. "Increased secretion of tumor necrosis factor α, interleukin 1, and interleukin 6 by human mononuclear cells exposed to β-galactoside-specific lectin from clinically applied mistletoe extract." Cancer research 50.11 (1990): 3322-3326.
  5.  Hoessli DC, Ahmad I. Mistletoe lectins: carbohydrate-specific apoptosis inducers and immunomodulators. Curr Org Chem. 2008;12(11):918–25;
  6. Büssing, A., et al. "Development of lymphocyte subsets in tumor patients after subcutaneous administration of mistletoe extracts." Forschende Komplementarmedizin 6.4 (1999): 196-204.
  7.  Hajto, Tibor. "Immunomodulatory effects of iscador: a Viscum album preparation." Oncology 43.Suppl. 1 (1986): 51-65.
  8.  Yoon, Taek Joon, et al. "Cellular and humoral adjuvant activity of lectins isolated from Korean mistletoe (Viscum album colaratum)." International Immunopharmacology 1.5 (2001): 881-889.
  9.  Enesel, Mircea Bogdan, et al. "Perioperative application of the Viscum album extract Isorel in digestive tract cancer patients." Anticancer research 25.6C (2005): 4583-4590; Büssing, Arndt, et al. "Prevention of surgery-induced suppression of granulocyte function by intravenous application of a fermented extract from Viscum album L. in breast cancer patients." Anticancer research 25.6C (2005): 4753-4757; Schink, Michael, et al. "Mistletoe extract reduces the surgical suppression of natural killer cell activity in cancer patients. A randomized phase III trial." Complementary Medicine Research 14.1 (2007): 9-17.
  10.  Kim, Jong-Jin, et al. "Enhanced dendritic cell maturation by the B-chain of Korean mistletoe lectin (KML-B), a novel TLR4 agonist." International Immunopharmacology 21.2 (2014): 309-319.
  11.  Steinborn, Carmen, et al. "Viscum album neutralizes tumor-induced immunosuppression in a human in vitro cell model." PLoS One 12.7 (2017): e0181553.
  12.  Saha, Chaitrali, et al. "Viscum album-mediated COX-2 inhibition implicates destabilization of COX-2 mRNA." PLoS One 10.2 (2015): e0114965.
  13.  Ćebović, Tatyana, Slavica Spasić, and Mira Popović. "Cytotoxic effects of the Viscum album L. extract on Ehrlich tumour cells in vivo." Phytotherapy research 22.8 (2008): 1097-1103.
  14.  Park, Yu-Kyoung, Young Rok Do, and Byeong-Churl Jang. "Apoptosis of K562 leukemia cells by Abnobaviscum F®, a European mistletoe extract." Oncology reports 28.6 (2012): 2227-2232.
  15.  Han, Seung-Yeon, et al. "Anti-cancer effects of enteric-coated polymers containing mistletoe lectin in murine melanoma cells in vitro and in vivo." Molecular and cellular biochemistry 408.1 (2015): 73-87.
  16.  Thronicke, Anja, et al. "Clinical safety of combined targeted and Viscum album L. therapy in oncological patients." Medicines 5.3 (2018): 100.
  17.  Brandenberger, Mathias, et al. "An exploratory study on the quality of life and individual coping of cancer patients during mistletoe therapy." Integrative Cancer Therapies 11.2 (2012): 90-100.
  18.  Kienle, Gunver S., and Helmut Kiene. "Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies." Integrative cancer therapies 9.2 (2010): 142-157.