Taraxacum officinale extract induces antitumorigenic effects in ovarian carcinoma cell lines

Purpose of Investigation: Patients suffering from ovarian cancer often use mistletoe preparations in combination with Taraxacum officinale (dandelion) extracts as supplementary therapy to conventional medicine. However, scientific data concerning antitumorigenic effects of Taraxacum extracts and co-treatment with mistletoe extracts are insufficient. Materials and Methods: Sensitivity of cancer cell lines towards a Taraxacum extract was determined by cell viability assays. Effects of Taraxacum on cell proliferation, cell cycle distribution, mitochondrial integrity, as well as migration and invasion were investigated in ovarian carcinoma cells (NIH:OVCAR-3 and SKOV-3). Results: Taraxacum extract caused a reduction of cell viability in a panel of adult cancer cell lines (cervical-, colon-, endometrial-, hepatocellular-, lung-, mamma-, ovarian-, pancreatic-, and urinary bladder carcinoma), whereby gynecological tumors were particularly susceptible. Inhibitory effects on cell viability, migration, mitochondrial integrity, and induction of apoptosis were observed in ovarian cancer cells. Combined therapy with mistletoe extracts revealed synergistic effects. Conclusion: This study provides first preclinical data on the antitumorigenic effects of Taraxacum and demonstrates the effectiveness of a combination treatment with mistletoe extracts in ovarian cancer cells.

Anthroposophic remedy; Gynecological tumors; Phytotherapy; Viscum album; Taraxacum officinale

[1] Banks E., Beral V., Reeves G.: “The epidemiology of epithelial ovarian cancer: A review”. Int. J. Gynecol. Cancer, 1997, 7, 425.

[2] Hoskins W.J. (ed). Principles and practice of gynecologic oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2014.

[3] Goff B.A., Mandel L., Muntz H.G., Melancon C.H.: “Ovarian carcinoma diagnosis”. Cancer, 2000, 89, 2068.

[4] Ozols R.F.: “Epithelial ovarian cancer”. In: Hoskins W.J. (ed). Principles and practice of gynecologic oncology. Philadelphia: Lippincott Williams & Wilkins, 2014, 1.

[5] Navo M.A., Phan J., Vaughan C., Palmer J.L., Michaud L., Jones K.L., et al.: “An assessment of the utilization of complementary and alternative medication in women with gynecologic or breast malignancies”. J. Clin. Oncol., 2004, 22, 671.

[6] Piao B.K., Wang Y.X., Xie G.R., Mansmann U., Matthes H., Beuth J., Lin H.S.: “Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial”. Anticancer Res., 2004, 24, 303.

[7] Troger W., Galun D., Reif M., Schumann A., Stankovic N., Milicevic M.: “Viscum album L. extract therapy in patients with locally advanced or metastatic pancreatic cancer: a randomised clinical trial on overall survival”. Eur. J. Cancer, 2013, 49, 3788.

[8] Endo Y., Tsurugi K., Franz H.: “The site of action of the A-chain of mistletoe lectin I on eukaryotic ribosomes The RNA N -glycosidase activity of the protein”. FEBS Lett., 1988, 231, 378.

[9] Jung M-L., Baudino S., Ribéreau-Gayon G., Beck J-P.: “Character- ization of cytotoxic proteins from mistletoe (Viscum album L.)”. Cancer Lett., 1990, 51, 103.

[10] Maris B.: “Frauenheilkunde und Geburtshilfe: Grundlagen und therapeutische Konzepte der Anthroposophischen Medizin”. 1st ed. Berlin: Salumed-Verl., 2012, X, 252 S.

[11] [Internet]. Available at: https://www.bfarm.de/SharedDocs/Downloads/DE/Arzneimittel/Zulassung/zulassungsarten/besTherap/am-Trad/indikatlistepara109-040824.pdf? blob=publicationFile&v=3

[12] Sigstedt S.C., Hooten C.J., Callewaert M.C., Jenkins A.R., Romero A.E., Pullin M.J., et al.: “Evaluation of aqueous extracts of Taraxacum officinale on growth and invasion of breast and prostate cancer cells”. Int. J. Oncol., 2008, 32, 1085.

[13] van Trinh N., Dang ND-P., Tran D.H., van Pham P.: “Taraxacum officinale dandelion extracts efficiently inhibited the breast cancer stem cell proliferation”. Biomed. Res. Ther., 2016, 3, 733.

[14] Koo H-N., Hong S-H., Song B-K., Kim C-H., Yoo Y-H., Kim H-M.: “Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells”. Life Sci., 2004, 74, 1149.

[15] Chatterjee S.J., Ovadje P., Mousa M., Hamm C., Pandey S.: “The efficacy of dandelion root extract in inducing apoptosis in drug-resistant human melanoma cells”. Evid. Based Complement. Alternat. Med., 2011, 2011, 129045.

[16] Choi E.J.: “Dandelion (Taraxacum officinale) Flower Ethanol Extract Inhibits Cell Proliferation and Induces Apoptosis in Human Ovarian Cancer SK-OV-3 Cells”. Food Sci. Biotechnol., 2009, 18, 552.

[17] Mosmann T.: “Rapid colorimetric assay for cellular growth and sur- vival: application to proliferation and cytotoxicity assays”. J. Immunol. Methods, 1983, 65, 55.

[18] Ke N.: “The xCELLigence System for Real-Time and Label-Free Monitoring of Cell Viability”. In: Stoddart M.J., (ed). Mammalian cell viability, Methods and protocols. New York, Humana Pr, 2011, 740, 33.

[19] Liang C-C., Park A.Y., Guan J-L.: “In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro”. Nat. Protoc., 2007, 2, 329.

[20] Cimmino F., Schulte J.H., Zollo M., Koster J., Versteeg R., Iolascon A., Eggert A., Schramm A.: “Galectin-1 is a major effector of TrkB-mediated neuroblastoma aggressiveness”. Oncogene, 2009, 28, 2015.

[21] Collins T.J.: “ImageJ for microscopy”. Biotechniques, 2007, 43, 25.

[22] Chou T-C.: “Drug combination studies and their synergy quantification using the Chou-Talalay method”. Cancer Res., 2010, 70, 440.

[23] Chou T.C., Talalay P.: “Quantitative analysis of dose-effect relation- ships: the combined effects of multiple drugs or enzyme inhibitors”. Adv. Enzyme Regul., 1984, 22, 27.

[24] Chou T-C.: “Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies”. Pharmacol Rev., 2006, 58, 621.

[25] Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., et al.: “Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012”. Int. J. Cancer, 2015, 136, E359.

[26] Brinton L.A.: “Epidemiology of Gynecologic Cancers”. In: Barakat R.R., Berchuk A., Markman M., Randall M.E. (eds). Principles and practice of gynecologic oncology. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Heath, 2013, 1.

[27] McKeage M.J.: “Comparative adverse effect profiles of platinum drugs”. Drug Saf., 1995, 13, 228.

[28] McWhinney S.R., Goldberg R.M., McLeod H.L.: “Platinum neuro-toxicity pharmacogenetics”. Mol. Cancer Ther., 2009, 8, 10.

[29] Grossarth-Maticek R., Ziegler R.: “Prospective Controlled Cohort Studies on Long-term Therapy of Ovarian Cancer Patients with Mistletoe (Viscum album L.) Extracts Iscador”. Arzneimittelforschung, 2007, 57, 665.

[30] Ostermann T., Raak C., Büssing A.: “Survival of cancer patients treated with mistletoe extract (Iscador): a systematic literature review”. BMC Cancer, 2009, 9, 451.

[31] Horneber M.A., Bueschel G., Huber R., Linde K., Rostock M.: “Mistletoe therapy in oncology”. Cochrane Database Syst. Rev., 2008, 2, CD003297.

[32] Levy AS-A., Stupack D.G.: “Cytotoxic activity of Taraxacum officinale in OV2008 human ovarian cancer cell line is mediated by caspase 8 activity”. FASEB J., 2010, 24, 965.

[33] Ovadje P., Ammar S., Guerrero J-A., Arnason J.T., Pandey S.: “Dandelion root extract affects colorectal cancer proliferation and survival through the activation of multiple death signalling pathways”. Oncotarget, 2016, 7, 73080.

[34] Ovadje P., Chatterjee S., Griffin C., Tran C., Hamm C., Pandey S.: “Selective induction of apoptosis through activation of caspase-8 in human leukemia cells (Jurkat) by dandelion root extract”. J. Ethnopharmacol., 2011, 133, 86.

[35] Ovadje P., Chochkeh M., Akbari-Asl P., Hamm C., Pandey S.: “Selective induction of apoptosis and autophagy through treatment with dandelion root extract in human pancreatic cancer cells”. Pancreas, 2012, 41, 1039.

[36] Ovadje P., Hamm C., Pandey S.: “Efficient induction of extrinsic cell death by dandelion root extract in human chronic myelomonocytic leukemia (CMML) cells”. PLoS One, 2012, 7, e30604.

[37] van Trinh N., Doan-Phuong Dang N., Hong Tran D., van Pham P.: “Taraxacum officinale dandelion extracts efficiently inhibited the breast cancer stem cell proliferation”. Biomed. Res. Ther., 2016, 3, 34.

[38] Kobayashi M., Salomon C., Tapia J., Illanes S.E., Mitchell M.D., Rice G.E.: “Ovarian cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 miRNA and miR-200”. J. Transl. Med., 2014, 12, 4.