A natural combination extract of viscum album L. containing both triterpene acids and lectins is highly effective against AML in Vivo

PLoS ONE

Volumn 10, Issue 8, 2015, Pages

  Delebinski, Catharina I ^a   Twardziok, Monika ^a   Kleinsimon, Susann ^a   Hoff, Florian ^b   Mulsow, Katharina ^c   Rolff, Jana ^d   Jäger, Sebastian ^e   Eggert, Angelika ^a   Seifert, Georg ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b PHILIPPS UNIVERSITY MARBURG   (Germany)

^c FREIE UNIVERSITÄT BERLIN   (Germany)

^d EPO GmbH Berlin Buch   (Germany)

^e Birken AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 8; CASPASE 9; CYTARABINE; CYTOCHROME C; DEATH RECEPTOR 4; DEATH RECEPTOR 5; LECTIN; MISTLETOE LECTIN I; OLEANOLIC ACID; PROTEIN BCL 2; TRITERPENE; UNCLASSIFIED DRUG; VISCUM ALBUM EXTRACT; WATER; ANTINEOPLASTIC AGENT; IL2RG PROTEIN, MOUSE; INTERLEUKIN 2 RECEPTOR GAMMA; PLANT EXTRACT; PLANT LECTIN;

ACUTE MYELOBLASTIC LEUKEMIA; ADOLESCENT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CASE REPORT; CELL MEMBRANE DEPOLARIZATION; CHILD; CONCENTRATION RESPONSE; DOWN REGULATION; DRUG EFFICACY; DRUG POTENTIATION; DRUG TOLERABILITY; ENZYME ACTIVITY; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; MALE; MITOCHONDRIAL MEMBRANE POTENTIAL; MOUSE; NONHUMAN; PROTEIN INDUCTION; PROTEIN SYNTHESIS; SCHOOL CHILD; TUMOR VOLUME; VISCUM ALBUM; ANIMAL; CELL PROLIFERATION; CHEMISTRY; DEFICIENCY; DOSE RESPONSE; DRUG EFFECTS; DRUG SCREENING; GENETICS; HL-60 CELL LINE; KNOCKOUT MOUSE; LEUKEMIA, MYELOID, ACUTE; NONOBESE DIABETIC MOUSE; PATHOLOGY; SCID MOUSE; TUMOR CELL CULTURE; U-937 CELL LINE;

ADOLESCENT; ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; CELL PROLIFERATION; CHILD; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HL-60 CELLS; HUMANS; INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT; LEUKEMIA, MYELOID, ACUTE; MALE; MICE, INBRED NOD; MICE, KNOCKOUT; MICE, SCID; OLEANOLIC ACID; PLANT EXTRACTS; PLANT LECTINS; TRITERPENES; TUMOR BURDEN; TUMOR CELLS, CULTURED; U937 CELLS; VISCUM ALBUM; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84941992249     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0133892     Document Type: Article

References (86)

1. Society AC. American Cancer Society: Cancer Facts and Figures 2014. American Cancer Society, available online. 2014.
2. Ahmad R, Liu S, Weisberg E, Nelson E, Galinsky I, Meyer C, et al. Combining the FLT3 inhibitor PKC412 and the triterpenoid CDDO-Me synergistically induces apoptosis in acute myeloid leukemia with the internal tandem duplication mutation. Molecular cancer research: MCR. 2010; 8(7):986-93. Epub 2010/06/24. doi: 10.1158/1541-7786.MCR-10-0154 PMID: 20571062; PubMed Central PMCID: PMC2905481.
3. Li W, Ding Y, Sun YN, Yan XT, Yang SY, Choi CW, et al. Oleanane-type triterpenoid saponins from the roots of Pulsatilla koreana and their apoptosis-inducing effects on HL-60 human promyelocytic leukemia cells. Archives of pharmacal research. 2013; 36(6):768-74. Epub 2013/03/05. doi: 10.1007/ s12272-013-0042-5 PMID: 23456692.
4. Huang Y, Li Y, Li XZ, Liu S, Lei P, Xiao J. [Study on the release of oleanolic acid loaded nanocapsules in vitro]. Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials. 2008; 31(2):283-5. Epub 2008/07/16. PMID: 18619279.
5. Xiao YJ, Chen YZ, Chen BH, Chen JH, Lin ZX, Fan YL. [Study on cytotoxic activities on human leukemia cell line HL-60 by flavonoids extracts of Scurrula parasitica from four different host trees]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. 2008; 33(4):427-32. Epub 2008/06/07. PMID: 18533504.
6. Schad F, Atxner J, Buchwald D, Happe A, Popp S, Kroz M, et al. Intratumoral Mistletoe (Viscum album L) Therapy in Patients With Unresectable Pancreas Carcinoma: A Retrospective Analysis. Integrative cancer therapies. 2013; 13(4):332-40. Epub 2013/12/24. doi: 10.1177/1534735413513637 PMID: 24363283.
7. Marvibaigi M, Supriyanto E, Amini N, Abdul Majid FA, Jaganathan SK. Preclinical and Clinical Effects of Mistletoe against Breast Cancer. BioMed research international. 2014; 2014:785479. Epub 2014/08/ 20. doi: 10.1155/2014/785479 PMID: 25136622; PubMed Central PMCID: PMC4127267.
8. Franz H, Ziska P, Kindt A. Isolation and properties of three lectins from mistletoe (Viscum album L.). BiochemJ. 1981; 195(2):481-4.
9. Orhan DD, Kupeli E, Yesilada E, Ergun F. Anti-inflammatory and antinociceptive activity of flavonoids isolated from Viscum album ssp. album. ZNaturforschC. 2006; 61(1-2):26-30.
10. Amer B, Juvik OJ, Francis GW, Fossen T. Novel GHB-derived natural products from European mistletoe (Viscum album). Pharmaceutical biology. 2013; 51(8):981-6. Epub 2013/06/06. doi: 10.3109/ 13880209.2013.773520 PMID: 23734579.
11. Nhiem NX, Kiem PV, Minh CV, Kim N, Park S, Lee HY, et al. Diarylheptanoids and flavonoids from viscum album inhibit LPS-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells. Journal of natural products. 2013; 76(4):495-502. Epub 2013/03/15. doi: 10.1021/ np300490v PMID: 23484668.
12. Jung ML, Baudino S, Ribereau-Gayon G, Beck JP. Characterization of cytotoxic proteins from mistletoe (Viscum album L.). Cancer Lett. 1990; 51(2):103-8. PMID: 2344587
13. Bussing A. Biological and pharmacological properties of Viscum album L. Mistletoe-The Genus Viscum 2000. p. 123-82.
14. Schaller G, Urech K, Grazi G, Giannattasio M. Viscotoxin composition of the three European subspecies of Viscum album. Planta Med. 1998; 64(7):677-8. PMID: 17253311
15. Urech K, Schaller G, Jaggy C. Viscotoxins, mistletoe lectins and their isoforms in mistletoe (Viscum album L.) extracts Iscador. Arzneimittelforschung. 2006; 56(6A):428-34. PMID: 16927522
16. Hajto T, Fodor K, Perjesi P, Nemeth P. Difficulties and Perspectives of Immunomodulatory Therapy with Mistletoe Lectins and Standardized Mistletoe Extracts in Evidence-based Medicine. EvidBased- Complement AlternatMed. 2009.
17. Tabiasco J, Pont F, Fournie JJ, Vercellone A. Mistletoe viscotoxins increase natural killer cell-mediated cytotoxicity. EurJBiochem. 2002; 269(10):2591-600.
18. Simon MM, Simard JC, Girard D. Viscum album agglutinin-I (VAA-I) increases cell surface expression of cytoskeletal proteins in apoptotic human neutrophils: moesin and ezrin are two novel targets of VAAI. Human & experimental toxicology. 2013; 32(10):1097-106. Epub 2012/12/25. doi: 10.1177/ 0960327112468910 PMID: 23263853.
19. Bussing A, Vervecken W, Wagner M, Wagner B, Pfuller U, Schietzel M. Expression of mitochondrial Apo2.7 molecules and caspase-3 activation in human lymphocytes treated with the ribosome-inhibiting mistletoe lectins and the cell membrane permeabilizing viscotoxins. Cytometry. 1999; 37(2):133-9. PMID: 10486525
20. Bussing A, Suzart K, Bergmann J, Pfuller U, Schietzel M, Schweizer K. Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins. Cancer Lett. 1996; 99- (1):59-72. PMID: 8564930
21. Bantel H, Engels IH, 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):2083-90. PMID: 10232592
22. Park HJ, Hong JH, Kwon HJ, Kim Y, Lee KH, Kim JB, et al. TLR4-mediated activation of mouse macrophages by Korean mistletoe lectin-C (KML-C). Biochemical and biophysical research communications. 2010; 396(3):721-5. Epub 2010/05/11. doi: 10.1016/j.bbrc.2010.04.169 PMID: 20450885.
23. Duong Van Huyen JP, Delignat S, Bayry J, Kazatchkine MD, Bruneval P, Nicoletti A, et al. Interleukin- 12 is associated with the in vivo anti-tumor effect of mistletoe extracts in B16 mouse melanoma. Cancer Lett. 2006; 243(1):32-7. PMID: 16412563
24. Klingbeil MF, Xavier FC, Sardinha LR, Severino P, Mathor MB, Rodrigues RV, et al. Cytotoxic effects of mistletoe (Viscum album L.) in head and neck squamous cell carcinoma cell lines. Oncology reports. 2013; 30(5):2316-22. Epub 2013/09/13. doi: 10.3892/or.2013.2732 PMID: 24026291.
25. Park YK, Do YR, Jang BC. Apoptosis of K562 leukemia cells by Abnobaviscum F(R), a European mistletoe extract. Oncology reports. 2012; 28(6):2227-32. Epub 2012/09/14. doi: 10.3892/or.2012.2026 PMID: 22972372.
26. Seifert G, Jesse P, Laengler A, Reindl T, Luth M, Lobitz S, et al. Molecular mechanisms of mistletoe plant extract-induced apoptosis in acute lymphoblastic leukemia in vivo and in vitro. Cancer Lett. 2008; 264(2):218-28. doi: 10.1016/j.canlet.2008.01.036 PMID: 18314258
27. Fulda S, Jeremias I, Steiner HH, Pietsch T, Debatin KM. Betulinic acid: a new cytotoxic agent against malignant brain-tumor cells. IntJCancer. 1999; 82(3):435-41.
28. Laszczyk MN. Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy. Planta Med. 2009; 75(15):1549-60. doi: 10.1055/s-0029-1186102 PMID: 19742422
29. Zhang W, Men X, Lei P. Review on anti-tumor effect of triterpene acid compounds. Journal of cancer research and therapeutics. 2014; 10 Suppl:C14-9. Epub 2014/09/11. doi: 10.4103/0973-1482.139746 PMID: 25207885.
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(2):157-62. PMID: 17415876
31. Ovesna Z, Vachalkova A, Horvathova K, Tothova D. Pentacyclic triterpenoic acids: new chemoprotective compounds. Minireview. Neoplasma. 2004; 51(5):327-33. PMID: 15640935
32. Fulda S, Debatin KM. Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors. MedPediatrOncol. 2000; 35(6):616-8.
33. Safayhi H, Sailer ER. Anti-inflammatory actions of pentacyclic triterpenes. Planta Med. 1997; 63- (6):487-93. PMID: 9434597
34. Assefa H, Nimrod A, Walker L, Sindelar R. Synthesis and evaluation of potential complement inhibitory semisynthetic analogs of oleanolic acid. BioorgMedChemLett. 1999; 9(14):1889-94.
35. Deeb D, Gao X, Jiang H, Dulchavsky SA, Gautam SC. Oleanane triterpenoid CDDO-Me inhibits growth and induces apoptosis in prostate cancer cells by independently targeting pro-survival Akt and mTOR. Prostate. 2009; 69(8):851-60. doi: 10.1002/pros.20937 PMID: 19189297
36. Deeb D, Gao X, Liu Y, Varma NR, Arbab AS, Gautam SC. Inhibition of telomerase activity by oleanane triterpenoid CDDO-Me in pancreatic cancer cells is ROS-dependent. Molecules. 2013; 18(3):3250-65. Epub 2013/03/15. doi: 10.3390/molecules18033250 PMID: 23486104; PubMed Central PMCID: PMC3632053.
37. Schaeffer P, Bernat A, Arnone M, Manara L, Gallas JF, Dol-Gleizes F, et al. Effect of SR58611A, a potent beta-3 adrenoceptor agonist, on cutaneous wound healing in diabetic and obese mice. European journal of pharmacology. 2006; 529(1-3):172-8. Epub 2005/12/06. doi: 10.1016/j.ejphar.2005. 11.005 PMID: 16325798.
38. Guo G, Yao W, Zhang Q, Bo Y. Oleanolic acid suppresses migration and invasion of malignant glioma cells by inactivating MAPK/ERK signaling pathway. PloS one. 2013; 8(8):e72079. Epub 2013/08/31. doi: 10.1371/journal.pone.0072079 PMID: 23991044; PubMed Central PMCID: PMC3749117.
39. Wang J, Yuan L, Xiao H, Xiao C, Wang Y, Liu X. Momordin Ic induces HepG2 cell apoptosis through MAPK and PI3K/Akt-mediated mitochondrial pathways. Apoptosis: an international journal on programmed cell death. 2013; 18(6):751-65. Epub 2013/02/19. doi: 10.1007/s10495-013-0820-z PMID: 23417763.
40. Baracchini C, Meneghetti G, Manara R, Ermani M, Ballotta E. Cerebral hemodynamics after contralateral carotid endarterectomy in patients with symptomatic and asymptomatic carotid occlusion: a 10- year follow-up. Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism. 2006; 26(7):899-905. Epub 2006/01/06. doi: 10.1038/sj. jcbfm.9600260 PMID: 16395290.
41. Konopleva M, Contractor R, Kurinna SM, Chen W, Andreeff M, Ruvolo PP. The novel triterpenoid CDDO-Me suppresses MAPK pathways and promotes p38 activation in acute myeloid leukemia cells. Leukemia. 2005; 19(8):1350-4. PMID: 15931262
42. Urech K, Scher JM, Hostanska K, Becker H. Apoptosis inducing activity of viscin, a lipophilic extract from Viscum album L. JPharmPharmacol. 2005; 57(1):101-9.
43. Pan S, Hu J, Zheng T, Liu X, Ju Y, Xu C. Oleanolic acid derivatives induce apoptosis in human leukemia K562 cell involved in inhibition of both Akt1 translocation and pAkt1 expression. Cytotechnology. 2014. Epub 2014/04/15. doi: 10.1007/s10616-014-9722-3 PMID: 24728886.
44. Gheorgheosu D, Duicu O, Dehelean C, Soica C, Muntean D. Betulinic acid as a potent and complex antitumor phytochemical: a minireview. Anti-cancer agents in medicinal chemistry. 2014; 14 (7):936-45. Epub 2014/02/27. PMID: 24568161.
45. Soica C, Danciu C, Savoiu-Balint G, Borcan F, Ambrus R, Zupko I, et al. Betulinic acid in complex with a gamma-cyclodextrin derivative decreases proliferation and in vivo tumor development of nonmetastatic and metastatic B164A5 cells. International journal of molecular sciences. 2014; 15- (5):8235-55. Epub 2014/05/14. doi: 10.3390/ijms15058235 PMID: 24821543; PubMed Central PMCID: PMC4057729.
46. Soica C, Oprean C, Borcan F, Danciu C, Trandafirescu C, Coricovac D, et al. The synergistic biologic activity of oleanolic and ursolic acids in complex with hydroxypropyl-gamma-cyclodextrin. Molecules. 2014; 19(4):4924-40. Epub 2014/04/22. doi: 10.3390/molecules19044924 PMID: 24747649.
47. Delebinski CI, Jaeger S, Kemnitz-Hassanin K, Henze G, Lode HN, Seifert GJ. A new development of triterpene acid-containing extracts from Viscum album L. displays synergistic induction of apoptosis in acute lymphoblastic leukaemia. Cell Prolif. 2012.
48. Struh CM, Jager S, Kersten A, Schempp CM, Scheffler A, Martin SF. Triterpenoids amplify anti-tumoral effects of mistletoe extracts onmurine B16.f10 melanoma in vivo. PloS one. 2013; 8(4):e62168. Epub 2013/04/25. doi: 10.1371/journal.pone.0062168 PMID: 23614029; PubMed Central PMCID: PMC3629099.
49. Li R, Quan P, Liu DF, Wei FD, Zhang Q, Xu QW. The influence of cosolvent on the complexation of HPbeta- cyclodextrins with oleanolic acid and ursolic acid. AAPSPharmSciTech. 2009; 10(4):1137-44.
50. Guo M, Zhang S, Song F, Wang D, Liu Z, Liu S. Studies on the non-covalent complexes between oleanolic acid and cyclodextrins using electrospray ionization tandem mass spectrometry. JMass Spectrom. 2003; 38(7):723-31.
51. Struh CM, Jager S, Schempp CM, Scheffler A, Martin SF. A Novel Triterpene Extract from Mistletoe Induces Rapid Apoptosis in Murine B16.F10 Melanoma Cells. PhytotherRes. 2012.
52. Jäger S, Trojan H, Kopp T, Laszczyk MN, Scheffler A. Pentacyclic Triterpene Distribution in Various Plants-Rich Sources for a New Group of Multi-Potent Plant Extracts. Molecules. 2009; 14:2016-31. doi: 10.3390/molecules14062016
53. Jaggy C, Musielski H, Urech K, Schaller G. Quantitative determination of lectins in mistletoe preparations. Arzneimittel-Forschung. 1995; 45(8):905-9. Epub 1995/08/01. PMID: 7575759.
54. GassmannM, Grenacher B, Rohde B, Vogel J. Quantifying Western blots: pitfalls of densitometry. Electrophoresis. 2009; 30(11):1845-55. Epub 2009/06/12. doi: 10.1002/elps.200800720 PMID: 19517440.
55. Kim MS, So HS, Lee KM, Park JS, Lee JH, Moon SK, et al. Activation of caspase cascades in Korean mistletoe (Viscum album var. coloratum) lectin-II-induced apoptosis of human myeloleukemic U937 cells. GenPharmacol. 2000; 34(5):349-55.
56. Montgomery C. Oncological and toxicological research: Alleviation and control of pain and distress in laboratory animals. Cancer Bulletin. 1990; 42:230-7.
57. Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995; 9(10):1783-6. Epub 1995/10/01. PMID: 7564526.
58. Webb RJ. Effect of more than one inhibitor. Enzyme and Metabolic Inhibitors. Academic Press, New York. 1963; 1:66-79-488-512.
59. MacEwen EG, Pastor J, Kutzke J, Tsan R, Kurzman ID, Thamm DH, et al. IGF-1 receptor contributes to the malignant phenotype in human and canine osteosarcoma. Journal of cellular biochemistry. 2004; 92(1):77-91. Epub 2004/04/20. doi: 10.1002/jcb.20046 PMID: 15095405.
60. Samudio I, Kurinna S, Ruvolo P, Korchin B, Kantarjian H, Beran M, et al. Inhibition of mitochondrial metabolism by methyl-2-cyano-3,12-dioxooleana-1,9-diene-28-oate induces apoptotic or autophagic cell death in chronic myeloid leukemia cells. MolCancer Ther. 2008; 7(5):1130-9.
61. Konopleva M, Elstner E, McQueen TJ, Tsao T, Sudarikov A, Hu W, et al. Peroxisome proliferatoractivated receptor gamma and retinoid X receptor ligands are potent inducers of differentiation and apoptosis in leukemias. MolCancer Ther. 2004; 3(10):1249-62.
62. Yates MS, Kwak MK, Egner PA, Groopman JD, Bodreddigari S, Sutter TR, et al. Potent protection against aflatoxin-induced tumorigenesis through induction of Nrf2-regulated pathways by the triterpenoid 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole. Cancer research. 2006; 66 (4):2488-94. Epub 2006/02/21. doi: 10.1158/0008-5472.CAN-05-3823 PMID: 16489057.
63. Yue P, Zhou Z, Khuri FR, Sun SY. Depletion of intracellular glutathione contributes to JNK-mediated death receptor 5 upregulation and apoptosis induction by the novel synthetic triterpenoid methyl-2- cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me). Cancer BiolTher. 2006; 5(5):492-7.
64. Petronelli A, Saulle E, Pasquini L, Petrucci E, Mariani G, Biffoni M, et al. High sensitivity of ovarian cancer cells to the synthetic triterpenoid CDDO-Imidazolide. Cancer Lett. 2009; 282(2):214-28. doi: 10. 1016/j.canlet.2009.03.018 PMID: 19364626
65. Zou W, Chen S, Liu X, Yue P, Sporn MB, Khuri FR, et al. c-FLIP downregulation contributes to apoptosis induction by the novel synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me) in human lung cancer cells. Cancer BiolTher. 2007; 6(10):1614-20.
66. Kluck RM, Martin SJ, Hoffman BM, Zhou JS, Green DR, Newmeyer DD. Cytochrome c activation of CPP32-like proteolysis plays a critical role in a Xenopus cell-free apoptosis system. The EMBO journal. 1997; 16(15):4639-49. Epub 1997/08/01. doi: 10.1093/emboj/16.15.4639 PMID: 9303308; PubMed Central PMCID: PMC1170090.
67. Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nature reviews Molecular cell biology. 2008; 9(1):47-59. Epub 2007/12/22. doi: 10.1038/nrm2308 PMID: 18097445.
68. Kim HK, Kim JE, Chung J, Park KH, Han KS, Cho HI. Lithium down-regulates the expression of CXCR4 in human neutrophils. J Trace Elem Med Biol. 2007; 21(3):204-9. Epub 2007/08/19. doi: 10.1016/j. jtemb.2007.03.001 PMID: 17697959.
69. Eckelman BP, Salvesen GS, Scott FL. Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO reports. 2006; 7(10):988-94. Epub 2006/10/04. doi: 10.1038/sj.embor. 7400795 PMID: 17016456; PubMed Central PMCID: PMC1618369.
70. Bi Y, Xu J, Sun F, Wu X, Ye W, Sun Y, et al. Synthesis and biological activity of 28-amide derivatives of 23-hydroxy betulinic Acid as antitumor agent candidates. Med Chem. 2013; 9(7):920-5. Epub 2012/10/ PMID: 23083117.
71. Lucio KA, Rocha Gda G, Moncao-Ribeiro LC, Fernandes J, Takiya CM, Gattass CR. Oleanolic acid initiates apoptosis in non-small cell lung cancer cell lines and reduces metastasis of a B16F10 melanoma model in vivo. PloS one. 2011; 6(12):e28596. Epub 2011/12/17. doi: 10.1371/journal.pone.0028596 PMID: 22174843; PubMed Central PMCID: PMC3235133.
72. Wei J, Liu H, Liu M, Wu N, Zhao J, Xiao L, et al. Oleanolic acid potentiates the antitumor activity of 5- fluorouracil in pancreatic cancer cells. Oncology reports. 2012; 28(4):1339-45. Epub 2012/07/25. doi: 10.3892/or.2012.1921 PMID: 22825128.
73. Shishodia S, Sethi G, Konopleva M, Andreeff M, Aggarwal BB. A synthetic triterpenoid, CDDO-Me, inhibits IkappaBalpha kinase and enhances apoptosis induced by TNF and chemotherapeutic agents through down-regulation of expression of nuclear factor kappaB-regulated gene products in human leukemic cells. ClinCancer Res. 2006; 12(6):1828-38.
74. Gao X, Liu Y, Deeb D, Liu P, Liu A, Arbab AS, et al. ROS mediate proapoptotic and antisurvival activity of oleanane triterpenoid CDDO-Me in ovarian cancer cells. Anticancer research. 2013; 33(1):215-21. Epub 2012/12/26. PMID: 23267148; PubMed Central PMCID: PMC3711076.
75. Ryu K, Susa M, Choy E, Yang C, Hornicek FJ, Mankin HJ, et al. Oleanane triterpenoid CDDO-Me induces apoptosis in multidrug resistant osteosarcoma cells through inhibition of Stat3 pathway. BMC cancer. 2010; 10:187. Epub 2010/05/13. doi: 10.1186/1471-2407-10-187 PMID: 20459702; PubMed Central PMCID: PMC2874784.
76. Dutta J, Fan Y, Gupta N, Fan G, Gelinas C. Current insights into the regulation of programmed cell death by NF-kappaB. Oncogene. 2006; 25(51):6800-16. Epub 2006/10/31. doi: 10.1038/sj.onc. 1209938 PMID: 17072329.
77. Cho HJ, Na KJ, Kim do W, Choi YE, Ma JS, Jeong IS. Chemical pleurodesis using a Viscum album extract in infants with congenital chylothorax. European journal of pediatrics. 2014; 173(6):823-6. Epub 2014/02/28. doi: 10.1007/s00431-014-2283-9 PMID: 24573572.
78. Hengst L, Reed SI. Translational control of p27Kip1 accumulation during the cell cycle. Science. 1996; 271(5257):1861-4. Epub 1996/03/29. PMID: 8596954.
79. Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T, Hannon GJ. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature. 1995; 377(6549):552-7. Epub 1995/10/12. doi: 10.1038/377552a0 PMID: 7566157.
80. Yu Q, Liu Y, Wang C, Sun D, Yang X, Liu J. Chiral ruthenium(II) polypyridyl complexes: stabilization of g-quadruplex DNA, inhibition of telomerase activity and cellular uptake. PloS one. 2012; 7(12):e50902. Epub 2012/12/14. doi: 10.1371/journal.pone.0050902 PMID: 23236402; PubMed Central PMCID: PMC3517606.
81. Ma H, Li J, Yang JJ, Tian WC, Liu H, Zhou YZ, et al. [Di-2-ethylhexyl phthalate and its metabolite single- ethylhexyl phthalate affect TGF-beta 1 expression and telomerase activity in the testis of young male rats]. Zhonghua nan ke xue = National journal of andrology. 2012; 18(9):783-8. Epub 2012/12/01. PMID: 23193663.
82. Bussing A, Multani AS, Pathak S, Pfuller U, Schietzel M. Induction of apoptosis by the N-acetylgalactosamine- specific toxic lectin from Viscum album L. is associated with a decrease of nuclear p53 and Bcl-2 proteins and induction of telomeric associations. Cancer Lett. 1998; 130(1-2):57-68. PMID: 9751257
83. Braun JM, Ko HL, Schierholz JM, Beuth J. Standardized mistletoe extract augments immune response and down-regulates local and metastatic tumor growth in murine models. Anticancer Res. 2002; 22- (6C):4187-90. PMID: 12553054
84. Hua Y, Zhang Z, Li J, Li Q, Hu S, Sun M, et al. Oleanolic acid derivative Dex-OA has potent anti-tumor and anti-metastatic activity on osteosarcoma cells in vitro and in vivo. Investigational new drugs. 2009.
85. Liby K, Risingsong R, Royce DB, Williams CR, Ma T, Yore MM, et al. Triterpenoids CDDO-methyl ester or CDDO-ethyl amide and rexinoids LG100268 or NRX194204 for prevention and treatment of lung cancer in mice. Cancer PrevRes(Phila). 2009; 2(12):1050-8.
86. Yamai H, Sawada N, Yoshida T, Seike J, Takizawa H, Kenzaki K, et al. Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo. IntJCancer. 2009; 125(4):952-60.