Mistletoe in the treatment of malignant melanoma

Year 2014, , 145 - 152, 01.03.2014

Esin Sakallı Çetin Pınar Aslan Koşar Nurten Özçelik

https://doi.org/10.5799/ahinjs.01.2014.01.0380

Abstract

Malignant melanoma is a malignant neoplasia drives from melanocytes. Malignant melanoma, the most causing death, is seen in the third place at skin cancer. Malignant melanoma shows intrinsic resistance to chemotherapeutic agents and variability in the course of the disease which are distinct features separating from other solid tumors. These features prevent the development and standardization of non-surgical treatment models of malignant melanoma. Although there is a large number of chemotherapeutic agents used in the treatment of metastatic malignant melanoma, it hasn\'t been demonstrated the survival advantage of adjuvant treatment with chemotherapeutic agents. Because of the different clinical course of malignant melanoma, the disease is thought to be closely associated with immune system. Therefore, immunomodulatory therapy models were developed. Mistletoe stimulates the immune system by increasing the number and activity of dendritic cells, thus it has been shown to effect on tumor growth and metastasis of malignant melanoma patient. Outlined in this review are the recent developments in the understanding the role of mistletoe as a complementary therapy for malignant melanoma. J Clin Exp Invest 2014; 5 (1): 145-152

Keywords

Malignant melanoma, mistletoe, Viscum album

Malign melanomun tedavisinde ökse otunun yeri

Abstract

Melanoma melanositlerden köken alan malign tümördür. Deri kanserleri içinde 3. sıklıkta görülen melanoma en fazla ölüme neden olan kanser tipidir. Malign melanomu, diğer solid tümörlerden ayıran belirgin özellikleri, kemoterapötik ajanlara gösterdiği intrinsik direnç ve hastalık seyrinin değişkenliğidir. Bu özellikler, malign melanomda cerrahi dışı tedavi modellerinin geliştirilmesini ve standart hale getirilmesini engellemektedir. Metastatik malign melanom tedavisinde kullanılan çok sayıda kemoterapötik ajan olmasına rağmen bu ajanlar ile yapılan adjuvan tedavi çalışmalarında sağ kalım avantajı gösterilememiştir. Malign melanomun farklı klinik seyir göstermesi nedeniyle, hastalığın immun sistem ile yakından ilişkili olabileceği düşünülmektedir. Bu nedenle immunomodulatör tedavi modelleri geliştirilmiştir. Ökse otunun dendritik hücrelerin sayısını ve aktivitesini artırmak suretiyle immün sistemi uyardığı ve böylece malign melanomlu hastada tümör büyümesi ve metastazı üzerine etkili olduğu gösterilmiştir. Derlemede malign melanomun komplementer tedavisinde ökseotunun rolünün anlaşılmasına yönelik güncel gelişmeler özetlenmiştir.

Keywords

Malign melanom, ökse otu, viscum album

References

• Pópulo H, Soares P, Lopes JM. Insights into mela- noma: targeting the mTOR pathway for therapeutics. Expert Opin Ther Targets 2012;16:689-705.
• Kaplan MA, Küçüköner M, İnal A, Işıkdoğan A, Urakçı Z. Ovarian malignant melanoma presenting with hy- percalcemia and bone marrow infiltration: a case report and review of the literature. J Clin Exp Invest 2012;3:96-98.
• Goldszmid RS, Idoyaga J, Bravo AI, et al. Dendritic cells charged with apoptotic tumor cells induce long-lived protective CD4+ and CD8+ T cell immunity against B16 melanoma. J Immunol 2003;171:5940-5947.
• Ho VC, Sober AJ. Therapy for cutaneous melanoma. J Am Acad Dermatol 1990;22:159-177.
• Eigentler TK, Caroli UM, Radny P, et al. Palliative therapy of disseminated malignant melanoma: a sys- tematic review of 41 randomised clinical trials. Lancet Oncol 2003;4: 748-759.
• Edler L. Mistel in der Krebstherapie. Dtsch Arztebl 2004;101:44-49.
• Steuer-Vogt MK, Bonkowsky A, Ambrosch P, et al. The effect of an adjuvant mistletoe treatment pro- gramme in resected head and neck cancer patients: a randomised controlled clinical trial. Eur J Cancer 2000;37:23-31.
• Elluru SR, Duong van Huyen JP, Delignat S, et al. In- duction of maturation and activation of human dendrit- ic cells: A mechanism underlying the beneficial effect of Viscum album as complimentary therapy in cancer. BMC Cancer 2008;8:161.
• Bussing 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.
• Stein GM, Pfuller U, Schietzel M, Bussing A. Intracel- lular expression of IL-4 and inhibition of IFN-gamma by extracts from European mistletoe is related to in- duction of apoptosis. Anticancer Res 2000; 20:2987- 2994.
• Elluru S, Van Huyen JP, Delignat S, Prost F, Bayry J, Kazatchkine MD. Molecular mechanisms underly- ing the immunomodulatory effects of mistletoe (Vis- cum album L.) extracts Iscador. Arzneimittelforschung
• Maier G, Fiebig HH. Absence of tumor growth stimula- tion in a panel of 16 human tumor cell lines by mistle- toe extracts in vitro. Anticancer Drugs 2002;13:373- 379.
• Thies A, Nugel D, Pfuller U, et al. Influence of mistle- toe lectins and cytokines induced by them on cell pro- liferation of human melanoma cells in vitro. Toxicology 2005;207:105-116.
• Freudlsperger C, Thies A, Pfüller U, Schumacher U. The Proteasome Inhibitor Bortezomib Augments Anti-proliferative Effects of Mistletoe Lectin-I and the PPAR-γ Agonist Rosiglitazone in Human Melanoma Cells. Antıcancer Res. 2007;27:207-214
• Thies A, Dautel P, Meyer A, et al. Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model. Brit J Cancer 2008;98:106 - 112.
• Duong Van Huyen JP, Delignat S, Bayry J, et al. In- terleukin-12 is associated with the in vivo anti-tumor effect of mistletoe extracts in B16 mouse melanoma. Cancer Lett 2006;243:32-37.
• Thies A, Mauer S, Fodstad O, Schumacher U. Clini- cally proven markers of metastasis predict metastatic spread of human melanoma cells engrafted in scid mice. Br J Cancer 2007b;96: 609-616.
• Kirsch A. Successful Treatment of Metastatic Malig- nant Melanoma with Viscum album Extract (Iscador® M). J Altern Complement Med 2007;13:443-446.
• Engell-Noerregaard L, Hansen TH, Andersen MH, et al. Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: as- sessment of correlation between clinical response and vaccine parameters. Cancer Immunol Immuno- ther 2009;58:1-14.
• Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. Cancer J Clin 2010;60:277-300.
• Tsao H, Atkins MB, Sober AJ. Management of cuta- neous melanoma. N Engl J Med 2004;351:998-1012.
• Li W, Sanki A, Karim RZ, et al. The role of cell cycle regulatory proteins in the pathogenesis of melanoma. Pathology 2006;38:287-301.
• Markovic SN, Erickson LA, Rao RD, et al. Malignant melanoma in the 21st century, part 1: epidemiology, risk factors, screening, prevention, and diagnosis. Mayo Clin Proc 2007;82:364-380.
• El Marsafy S, Bagot M, Bensussan A, and Mauviel A. Dendritic cells in the skin—potential use for melanoma treatment. Pigment Cell Melanoma Res 2008;22:30- 41.
• Bajetta E, Del Vecchio M, Bernard-Marty C, et al. “Metastatic melanoma: chemotherapy,” Seminars in Oncology 2002;29:427-445.
• Mocellin S, Pasquali S, Rossi CR, Nitti D. Interferon alpha adjuvant therapy in patients with high-risk mela- noma: a systematic review and meta-analysis. J Natl Cancer Inst 2010;102:493-501.
• Graziani G, Tentori L, Navarra P. Ipilimumab: a novel immunostimulatory monoclonal antibody for the treat- ment of cancer. Pharmacol Res 2012;65:9-22.
• Karabulut B, Sezgin VC, Göksel G, et al. The Efficacy and Tolerability of Intermediate High Dose Interferon Alpha 2B Treatment as an Adjuvant Therapy of High Risk Malignant Melanoma. The Turk J Hematol and Oncol 2005;15:6-14.
• Kadison AS, Morton DL. Immunotherapy of malignant melanoma. Surg Clin North Am. 2003;83:343-70.
• Eggermont AM, Suciu S, Santinami M, et al. Adjuvant therapy with pegylated interferon alfa-2b versus ob- servation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet 2008;372:117-126.
• Hauschild A, Weichenthal M, Balda BR, et al. Pro- spective randomized trial of interferon alfa-2b and interleukin-2 as adjuvant treatment for resected in- termediate- and high-risk primary melanoma without clinically detectable node metastasis. J Clin Oncol 2003;21:2883-2888.
• Pectasides D, Dafni U, Bafaloukos D, et al. Ran- domized phase III study of 1 month versus 1 year of adjuvant high-dose interferon alfa-2b in patients with resected high-risk melanoma. J Clin Oncol 2009;27:939-944.
• Kilbridge KL, Cole BF, Kirkwood JM, et al. Quality- of-life-adjusted survival analysis of high-dose adju- vant interferon alpha-2b for high-risk melanoma pa- tients using intergroup clinical trial data. J Clin Oncol 2002;20:1311-1318.
• Eggermont AM, Voit C. Management of melanoma: a European perspective. Surg Oncol Clin N Am 2008;17:635-648.
• Ascierto PA, Kirkwood JM. Adjuvant therapy of mela- noma with interferon: lessons of the past decade. J Transl Med 2008;6:62.
• Dummer R, Hauschild A, Jost L. Cutaneous malig- nant melanoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008;19:86-88.
• Tuettenberg A, Schmitt E, Knop J, Jonuleit H. Dendrit- ic Cell-Based Immunotherapy of Malignant Melano- ma: Success and Limitations. JDDG 2007;5:190-196.
• Satthaporn S, Eremin O. Dendritic cells (I): Biological functions. J R Coll Surg Edinb 2001;46:9-19.
• Eggenschwiler J, von Balthazar L, Stritt B, et al. Mis- tletoe lectin is not the only cytotoxic component in fer- mented preparations of Viscum album from white fir (Abies pectinata). BMC Complement and Altern Med 2007;7:14
• Legnani W. Integrative Cancer Therapies. Anticancer Res 2008;28:1893-7
• Becker H: Botany ofEuropean mistletoe (Viscum al- bum L.). Oncology 1986;43:2-7.
• Lee CH, Kim JK, Kim HY, et al. Immunomodulating effects of Korean mistletoe lectin in vitro and in vivo. Int Immunopharmacol 2009;9:1555-1561.
• Deliorman D, Çalış İ, Ergun F, et al. “Studies on the vascular effects of the fractions and phenolic com- pounds isolated from Viscum album ssp. album”. J of Ethnopharmacology 2000;72:323-329.
• Yesilada E, Deliorman D, Ergun F, et al. Effects of the Turkish subspecies of Viscum album on macrophage- derived cytokines. J Ethnopharmacol 1998;61:195- 200.
• Maier G, Fiebig HH. Absence of tumor growth stimula- tion in a panel of 16 human tumor cell lines by mistle- toe extracts in vitro. Anticancer Drugs 2002;13:373- 379.
• Sakallı Çetin E, Özcelik N. Apoptotic mechanism of mistletoe (viscum album) extract used in the treat- ment of cancer: review. J Med Sci 2007;27:533-539.
• Horneber MA, Bueschel G, Huber R, et al. Mistletoe therapy in oncology. Cochrane Database Syst Rev 2008;16:CD003297.
• Ribéreau-Gayon G, Jung ML, Di Scala D, Beck JP. Comparison of the effects of fermented and unfer- mented mistletoe preparations on cultured tumor cells. Oncology 1986;43:35-41.
• Stauder H, Kreuser ED. Mistletoe extracts stan- dardised in terms of mistletoe lectins (ML I) in on- cology: current state of clinical research. Onkologie 2002;25:374-380.
• Hajto T, Hostanska K, Frei K, et al. Increased secre- tion of tumor necrosis factor-α interleukin-1, and in- terleukin-6 by human mononuclear cells exposed to the β-galactoside-specific lectin from clinically applied mistletoe extract. Cancer Res 1990;50:3322-3326.
• Hajto T, Hostanska K, Fischer J, Saller R. Immuno- modulatory effects of Viscum album agglutinin-I on natural immunity. Anticancer Drugs 1997;8:43-46.
• Schink M. Mistletoe therapy for human cancer: The role of the natural killer cells. Anticancer Drugs 1997;8:47-51.
• Pryme IF, Bardocz S, Pusztai A, Ewen SWB. Sup- pression of growth of tumour cell lines in vitro and in tumours in vivo by mistletoe lectins. Histol Histopathol 2006;21:285 -299.
• Orhan DD, Küpeli E, Yesilada E, Ergun F. Anti-inflam- matory and antinociceptive activity of flavonoids iso- lated from Viscum album ssp. album. Z Naturforsch C. 2006;61:26-30.
• Jager S, Winkler K, Pfuller U, Scheffler A. Solubility studies of oleanolic acid and betulinic acid in aqueous solutions and plant extracts of Viscum album L. Planta Med 2007;73:157-162.
• Bussing A, ed. Mistletoe. The Genus Viscum. Amster- dam, the Netherlands: Hardwood Academic; 2000.
• Bussing A, Suzart K, Bergmann J, et al. Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins. Cancer Lett 1996;99:59-72.
• Endo Y, Tsurugi K, Franz H. The site of action of the A-chain of mistletoe lectin I on eukaryotic ribosomes. FEBS Lett 1988;231:378-380.
• Stirpe F, Barbieri L, Battelli MG, et al. Ribosome inac- tivating proteins from plants: present status and future prospects. Biotechnology 1992;10:405-412.
• Barbieri L, Battelli MG, Stirpe F. Ribosome-inacti- vating proteins from plants. Biochem Biophys Acta 1993;1154:237- 282.
• Beuth J. Clinical relevance of immunoactive mistletoe lectin-I. Anticancer Drugs 1997;8:53-55.
• Thies A, Pfuller U, Schachner M, et al. Binding of mis- tletoe lectins to cutaneous malignant melanoma: im- plications for prognosis and therapy. Anticancer Res 2001;21:2883-2888.
• Thies A, Berlin A, Brunner G, et al. Glycoconjugate profiling of primary melanoma and its sentinel node and distant metastases: implications for diagnosis and pathophysiology of metastases. Cancer Lett 2007a;248: 68-80.
• Thies A, Nugel D, Pfüller U, et al. Influence of mistle- toe lectins and cytokines induced by them on cell pro- liferation of human melanoma cells in vitro. Toxicology 2005;207:105-116.
• Heinzerling L, Von Baehr V, Liebenthal C, et al. Im- munologic effector mechanisms of a standardized mistletoe extract on the function of human monocytes and lymphocytes in vitro, ex vivo, and in vivo. J Clin Immunol 2006; 26:347-359.
• Stein GM, Bussing A, Schietzel M. Activation of den- dritic cells by an aqueous mistletoe extract and mistle- toe lectin-3 in vitro. Anticancer Res 2002;22:267-274.
• Trinchieri G. Interleukin-12 and the regulation of in- nate resistance and adaptative immunity. Nat Rev Im- munol 2003;3:133-146.
• Hajto T, Hostanska K, Gabius HJ. Modulatory potency of the beta-galactoside-specific lectin from mistletoe extract (Iscador) on the host defense system in vivo in rabbits and patients. Cancer Res 1989;49:4803-4808.
• Gardin N.E. Immunological Response to Mistletoe (Viscum album L) in Cancer Patients: A Four-Case Series. Phytother Res 2008;23:407-411.
• Weber C, Mengs U, Schwarz T, et al. Effects of a standardized mistletoe preparation on metastatic B16 melanoma colonization in murine lungs. Drug Res