Nuphar lutea thioalkaloids inhibit the nuclear factor κB pathway, potentiate apoptosis and are synergistic with cisplatin and etoposide

Cancer Biology and Therapy

Volumn 8, Issue 19, 2009, Pages 1860-1868

  Ozer, Janet ^a   Eisner, Nadav ^a   Ostrozhenkova, Elena ^b   Bacher, Adelbert ^b   Eisenreich, Wolfgang ^b   Benharroch, Daniel ^c   Golan Goldhirsh, Avi ^a   Gopas, Jacob ^a,c  

^a BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^c BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

Author keywords

6 hydroxythiobinupharidine; 6 hydroxythiobinuphlutine B; Apoptosis; Dimeric sesquiterpene thioalkaloids; NF B; Nuphar

Indexed keywords

ALKALOID DERIVATIVE; CISPLATIN; ETOPOSIDE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NUPHAR LUTEA EXTRACT; PLANT EXTRACT; PROCASPASE 9; SESQUITERPENE; THIOALKALOID DERIVATIVE; THIONUPHARIDINE DERIVATIVE; THIONUPHLUTIDINE DERIVATIVE; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CELL STRAIN MCF 7; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG EFFECT; DRUG MECHANISM; DRUG POTENTIATION; HUMAN; HUMAN CELL; NUPHAR; NUPHAR LUTEA; PLANT LEAF; RHIZOME;

ALKALOIDS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; BREAST NEOPLASMS; CELL LINE, TUMOR; CISPLATIN; DRUG SYNERGISM; ETOPOSIDE; HODGKIN DISEASE; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; METHANOL; NF-KAPPA B; NUPHAR; PLANT EXTRACTS; SULFHYDRYL COMPOUNDS;

EID: 73549117661     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.8.19.9567     Document Type: Article

References (43)

1. Gilmore TD, Herscovitch M. Inhibitors of NFkappaB signaling: 785 and counting. Oncogene 2006; 25:6887-99.
2. Bonizzi G, Karin M. The two NFkappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 2004; 25:280-8.
3. Ghosh S, Karin M. Missing pieces in the NFkappaB puzzle. Cell 2002; 109:81-96.
4. Amit S, Ben-Neriah Y. NFkappaB activation in cancer: a challenge for ubiquitination- and proteasome-based therapeutic approach. Semin Cancer Biol 2003; 13:15-28.
5. Karin M. NFkappaB and cancer: mechanisms and targets. Mol Carcinog 2006; 45:355-61.
6. Joos S, Granzow M, Holtgreve-Grez H, Siebert R, Harder L, Martin-Subero JI, et al. Hodgkin's lymphoma cell lines are characterized by frequent aberrations on chromosomes 2p and 9p including REL and JAK2. Int J Cancer 2003; 103:489-95.
7. Rayet B, Gelinas C. Aberrant rel/nfkb genes and activity in human cancer. Oncogene 1999; 18:6938-47.
8. Davis RE, Brown KD, Siebenlist U, Staudt LM. Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med 2001; 194:1861-74.
9. Kordes U, Krappmann D, Heissmeyer V, Ludwig WD, Scheidereit C. Transcription factor NFkappaB is constitutively activated in acute lymphoblastic leukemia cells. Leukemia 2000; 14:399-402.
10. Bargou RC, Leng C, Krappmann D, Emmerich F, Mapara MY, Bommert K, et al. High-level nuclear NFkappaB and Oct-2 is a common feature of cultured Hodgkin/Reed-Sternberg cells. Blood 1996; 87:4340-7.
11. Izban KF, Ergin M, Huang Q, Qin JZ, Martinez RL, Schnitzer B, et al. Characterization of NFkappaB expression in Hodgkin's disease: inhibition of constitutively expressed NFkappaB results in spontaneous caspase-independent apoptosis in Hodgkin and Reed-Sternberg cells. Mod Pathol 2001; 14:297-310.
12. Krappmann D, Emmerich F, Kordes U, Scharschmidt E, Dorken B, Scheidereit C. Molecular mechanisms of constitutive NFkappaB/Rel activation in Hodgkin/Reed-Sternberg cells. Oncogene 1999; 18:943-53.
13. Wood KM, Roff M, Hay RT. Defective IkappaBalpha in Hodgkin cell lines with constitutively active NFkappaB. Oncogene 1998; 16:2131-9.
14. Bargou RC, Emmerich F, Krappmann D, Bommert K, Mapara MY, Arnold W, et al. Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells. J Clin Invest 1997; 100:2961-9.
15. Hinz M, Loser P, Mathas S, Krappmann D, Dorken B, Scheidereit C. Constitutive NFkappaB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells. Blood 2001; 97:2798-807.
16. Skinnider BF, Mak TW. The role of cytokines in classical Hodgkin lymphoma. Blood 2002; 99:4283-97.
17. Annunziata CM, Safiran YJ, Irving SG, Kasid UN, Cossman J. Hodgkin disease: pharmacologic intervention of the CD40-NFkappaB pathway by a protease inhibitor. Blood 2000; 96:2841-8.
18. Cabannes E, Khan G, Aillet F, Jarrett RF, Hay RT. Mutations in the IκBα gene in Hodgkin's disease suggest a tumour suppressor role for IkappaBalpha. Oncogene 1999; 18:3063-70.
19. Jungnickel B, Staratschek-Jox A, Brauninger A, Spieker T, Wolf J, Diehl V, et al. Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma. J Exp Med 2000; 191:395-402.
20. Benharroch D, Dima E, Levy A, Ohana-Malka O, Ariad S, Prinsloo I, et al. Differential expression of sialyl and non-sialyl-CD15 antigens on Hodgkin-Reed-Sternberg cells: significance in Hodgkin's disease. Leuk Lymphoma 2000; 39:185-94.
21. Ohana-Malka O, Benharroch D, Isakov N, Prinsloo I, Shubinsky G, Sacks M, Gopas J. Selectins and anti-CD15 (Lewis x/a) antibodies transmit activation signals in Hodgkin's lymphoma-derived cell lines. Exp Hematol 2003; 31:1057-65.
22. Abu-Ghanem S, Oberkovitz G, Benharroch D, Gopas J, Livneh E. PKCeta expression contributes to the resistance of Hodgkin's lymphoma cell lines to apoptosis. Cancer Biol Ther 2007; 6:1375-80.
23. Emmerich F, Theurich S, Hummel M, Haeffker A, Vry MS, Dohner K, et al. Inactivating IkappaBepsilon mutations in Hodgkin/Reed-Sternberg cells. J Pathol 2003; 201:413-20.
24. DiDonato JA, Mercurio F, Karin M. Phosphorylation of IkappaBalpha precedes but is not sufficient for its dissociation from NFkappaB. Mol Cell Biol 1995; 15:1302-11.
25. Sathiyamoorthy P, Lugasi-Evgi H, Van-Damme P, Abu-Rabia A, Gopas J, Golan-Goldhirsh A. Larvicidal activity in desert plants of the Negev and Bedouin market plant products. Int J Pharm 1997; 35:265-73.
26. Sathiyamoorthy P, Lugasi-Evgi H, Schlesinger P, Kedar I, Gopas J, Pollack Y, et al. Screening for cytotoxic and antimalarial activities in desert plants of the Negev and Bedouin market plant products. Pharm Biol 1999; 37:188-95.
27. Brkic G, Gopas J, Tanic N, Dedovic-Tanic N, Benharroch D, Finkelstein-Jaworowsky E, et al. Genomic instability in drug-resistant human melanoma cell lines detected by Alu-I-arbitrary-primed PCR. Anticancer Res 2003; 23:2601-8.
28. Tanic N, Brkic G, Dimitrijevic B, Dedovic-Tanic N, Gefen N, Benharroch D, Gopas J. Identification of differentially expressed mRNA transcripts in drug-resistant versus parental human melanoma cell lines. Anticancer Res 2006; 26:2137-42.
29. Yoshikawa M, Yamaguchi S, Matsuda H, Kohda Y, Ishikawa H, Tanaka N, et al. Crude drugs from aquatic plants IV. On the constituents of alismatis rhizoma (2). Stereostructures of bioactive sesquiterpenes, alismol, alismoxide, orientalols A, B and C, from Chinese alismatis rhizoma. Chem Pharm Bull 1994; 42:1813-6.
30. Dolcet X, Llobet D, Pallares J, Matias-Guiu X. NFκB in development and progression of human cancer. Virchows Arch 2005; 446:475-82.
31. Garg A, Aggarwal BB. Nuclear transcription factor-kappaB as a target for cancer drug development. Leukemia 2002; 16:1053-68.
32. Nakanishi C, Toi M. Nuclear factor-kappaB inhibitors as sensitizers to anticancer drugs. Nat Rev Cancer 2005; 5:297-309.
33. Neumann M, Naumann M. Beyond IkappaBs: alternative regulation of NFkappaB activity. Faseb J 2007; 21:2642-54.
34. Saccani S, Marazzi I, Beg AA, Natoli G. Degradation of promoter-bound p65/RelA is essential for the prompt termination of the nuclear factor kappaB response. J Exp Med 2004; 200:107-13.
35. Garcia-Pineres AJ, Lindenmeyer MT, Merfort I. Role of cysteine residues of p65/NFkappaB on the inhibition by the sesquiterpene lactone parthenolide and N-ethyl maleimide, and on its transactivating potential. Life Sci 2004; 75:841-56.
36. Mackenzie GG, Queisser N, Wolfson ML, Fraga CG, Adamo AM, Oteiza PI. Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NFkappaB and STAT3 pathways in Hodgkin's lymphoma cells. Int J Cancer 2008; 123:56-65.
37. Siedle B, Garcia-Pineres AJ, Murillo R, Schulte-Monting J, Castro V, Rungeler P, et al. Quantitative structure-activity relationship of sesquiterpene lactones as inhibitors of the transcription factor NFkappaB. J Med Chem 2004; 47:6042-54.
38. Matsuda H, Morikawa T, Oda M, Asao Y, Yoshikawa M. Potent anti-metastatic activity of dimeric sesquiterpene thioalkaloids from the rhizome of Nuphar pumilum. Bioorg Med Chem Lett 2003; 13:4445-9.
39. Michael JP. Indolizidine and quinolizidine alkaloids. Nat Prod Rep 2008; 25:139-65.
40. Matsuda H, Yoshida K, Miyagawa K, Nemoto Y, Asao Y, Yoshikawa M. Nuphar alkaloids with immediately apoptosis-inducing activity from Nuphar pumilum and their structural requirements for the activity. Bioorg Med Chem Lett 2006; 16:1567-73.
41. Modzelewska A, Sur S, Kumar SK, Khan SR. Sesquiterpenes: natural products that decrease cancer growth. Curr Med Chem Anticancer Agents 2005; 5:477-99.
42. Yamahara J, Shimoda H, Matsuda H, Yoshikawa M. Potent immunosuppressive principles, dimeric sesquiterpene thioalkaloids, isolated from nupharis rhizoma, the rhizoma of Nuphar pumilum (nymphaeaceae): structure-requirement of nuphar-alkaloid for immunosuppressive activity. Biol Pharm Bull 1996; 19:1241-3.
43. Sethi G, Ahn KS, Sung B, Aggarwal BB. Pinitol targets nuclear factor-kappaB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion and angiogenesis. Mol Cancer Ther 2008; 7:1604-14.