Cucurbitacin B, a novel in vivo potentiator of gemcitabine with low toxicity in the treatment of pancreatic cancer

British Journal of Pharmacology

Volumn 160, Issue 4, 2010, Pages 998-1007

  Iwanski, Gabriela B ^a   Lee, Dhong H ^a   En Gal, Shlomit ^a   Doan, Ngan B ^b   Castor, Brandon ^b   Vogt, Marco ^c   Toh, Melvin ^d   Bokemeyer, Carsten ^e   Said, Jonathan W ^b   Thoennissen, Nils H ^a   Koeffler, H Phillip ^a,f  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b Santa Monica UCLA Medical Center   (United States)

^c Asklepios Klinikum   (Germany)

^d (Holdings) Inc   (Hong Kong)

^e UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^f Dept Medicine Endocrinol Diabet   (Singapore)

Author keywords

Cucurbitacin B; Gemcitabine; JAK STAT pathway; Murine xenograft model; Pancreatic cancer

Indexed keywords

CASPASE; CUCURBITACIN B; GEMCITABINE; MYC PROTEIN; PROTEIN BCL 2; PROTEIN BCL XL; TRITERPENOID; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; APOPTOSIS REGULATORY PROTEIN; DEOXYCYTIDINE; MYC PROTEIN, HUMAN; TRITERPENE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; BLOOD CELL COUNT; BLOOD CHEMISTRY; CANCER CELL; CANCER INHIBITION; COLONY FORMATION; CONTROLLED STUDY; DRUG MEGADOSE; DRUG POTENTIATION; DRUG TOLERABILITY; ENZYME ACTIVATION; HISTOPATHOLOGY; HUMAN; HUMAN CELL; IN VIVO STUDY; LOW DRUG DOSE; MOUSE; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; TUMOR XENOGRAFT; VISCERA; WESTERN BLOTTING; ANALOGS AND DERIVATIVES; ANIMAL; BLOOD; BONE MARROW CELL; CELL PROLIFERATION; COMPARATIVE STUDY; DOSE RESPONSE; DRUG EFFECTS; DRUG SCREENING; FEMALE; METABOLISM; NUDE MOUSE; PANCREATIC NEOPLASMS; PATHOLOGY; STEM CELL; TUMOR CELL LINE; TUMOR VOLUME;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS REGULATORY PROTEINS; BONE MARROW CELLS; CELL LINE, TUMOR; CELL PROLIFERATION; DEOXYCYTIDINE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SYNERGISM; ENZYME ACTIVATION; FEMALE; HUMANS; MICE; MICE, NUDE; PANCREATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS C-MYC; STEM CELLS; TRITERPENES; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 77952869512     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2010.00741.x     Document Type: Article

References (33)

1. Amati B, Brooks MW, Levy N, Littlewood TD, Evan GI, Land H (1993). Oncogenic activity of the c-Myc protein requires dimerization with Max. Cell 72 : 233 245.
2. Ayer DE, Kretzner L, Eisenman RN (1993). Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell 72 : 211 222.
3. Blackwood EM, Lüscher B, Eisenman RN (1992). Myc and Max associate in vivo. Genes Dev 1 : 71 80.
4. Burris HA 3rd., Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR et al 1997). Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15 : 2403 2413.
5. Chen JC, Chiu MH, Nie RL, Cordell GA, Qiu SX (2005). Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat Prod Rep 22 : 386 399.
6. Haritunians T, Gueller S, Zhang L, Badr R, Yin D, Xing H et al 2008). Cucurbitacin B induces differentiation, cell cycle arrest, and actin cytoskeletal alterations in myeloid leukemia cells. Leuk Res 32 : 1366 1373.
7. Jayaprakasam B, Seeram NP, Nair MG (2003). Anticancer anti-inflammatory activities of cucurbitacins from Cucurbita andreana. Cancer Lett 189 : 11 16.
8. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T et al 2008). Cancer statistics 2008. CA Cancer J Clin 58 : 71 96.
9. Kindler HL, Niedzwiecki D, Hollis D, Oraefo E, Schrag D, Hurwitz H et al 2007). A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): a preliminary analysis of Cancer and Leukemia Group B (CALGB). J Clin Oncol ASCO 2007 Annual Meeting 25: 4508.
10. Lahoz EG, Xu L, Schreiber-Agus N, DePinho RA (1994). Suppression of Myc, but not E1a, transformation activity by Max-associated proteins, Mad and Mxi1. Proc Natl Acad Sci USA 91 : 5503 5507.
11. Langer R (1998). Drug delivery and targeting. Nature 392 : 5 10.
12. Levens DL (2003). Reconstructing MYC. Genes Dev 17 : 1071 1077.
13. Li CM, Margolin AA, Salas M, Memeo L, Mansukhani M, Hishoosh H et al 2006). PEG10 is a c-MYC target gene in cancer cells. Cancer Res 2 : 665 672.
14. Luong QT, O'Kelly J, Braunstein GD, Hershman JM, Koeffler HP (2006). Antitumor activity of suberoylanilide hydroxamic acid against thyroid cancer cell lines in vitro and in vivo. Clin Cancer Res 12 : 5570 5577.
15. Mitry E, Ducreux M, Ould-Kaci M, Boige V, Seitz JF, Bugat R et al 2006). Oxaliplatin combined with 5-FU in second line treatment of advanced pancreatic adenocarcinoma. Results of a phase II trial. Gastroenterol Clin Biol 30 : 357 363.
16. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S et al 2007). Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25 : 1960 1966.
17. Musza LL, Speight P, McElhiney S, Barrow CJ, Gillum AM, Cooper R et al 1994). Cucurbitacins, cell adhesion inhibitors from Conobea scoparioides. Nat Prod 57 : 1498 1502.
18. Oettle H, Pelzer U, Stieler J, Hilbig A, Roll L, Schwaner I et al 2005). Oxaliplatin/folinic acid/5-fluorouracil [24 h] (OFF) plus best supportive careversus best supportive care alone (BSC) in second-line therapy ofgemcitabine-refractory advanced pancreatic cancer (CONKO 003). J Clin Oncol ASCO Annual Meeting 2005 Proc (Post-Meeting Edition) 23: 4031.
19. Patel JH, Loboda AP, Showe MK, Showe LC, McMahon SB (2004). Analysis of genomic targets reveals complex functions of MYC. Nat Rev Cancer 4 : 562 568.
20. Pessina A, Malerba I, Gribaldo L (2005). Hematotoxicity testing by cell clonogenic assay in drug development and preclinical trials. Curr Pharm Des 11 : 1055 1065.
21. Sahu RP, Srivastava SK (2009). The Role of STAT-3 in the Induction of Apoptosis in Pancreatic Cancer Cells by Benzyl Isothiocyanate. J Natl Cancer Inst 101 : 176 193.
22. Schleger C, Verbeke C, Hildenbrand R, Zentgraf H Bleyl U (2002). c-MYC activation in primary and metastatic ductal adenocarcinoma of the pancreas: incidence, mechanisms, and clinical significance. Mod Pathol 15 : 462 469.
23. Solit DB, Zheng FF, Drobnjak M, Münster PN, Higgins B, Verbel D et al 2002). 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin Cancer Res 8 : 986 993.
24. Strimpakos A, Saif MW, Syrigos KN (2008). Pancreatic cancer: from molecular pathogenesis to targeted therapy. Cancer Metastasis Rev 27 : 495 522.
25. Sun FX, Tohgo A, Bouvet M, Yagi S, Nassirpour R, Moossa AR et al 2003). Efficacy of camptothecin analog DX-8951f (exatecan mesylate) on human pancreatic cancer in an orthotopic metastatic model. Cancer Res 63 : 80 85.
26. Thoennissen NH, Iwanski GB, En-Gal S, Okamoto R, Lin P, Abbassi S et al 2009). Cucurbitacin B induces apoptosis by inhibition of the JAK/STAT pathway and potentiates antiproliferative effects of gemcitabine on pancreatic cancer cells. Cancer Res 69 : 5876 5884.
27. Toyonaga T, Nakano K, Nagano M, Zhao G, Yamaguchi K, Kuroki S et al 2003). Blockade of constitutively activated Janus kinase/signal transducer and activator of transcription-3 pathway inhibits growth of human pancreatic cancer. Cancer Lett 201 : 107 116.
28. Vulfovich M, Rocha-Lima C (2008). Novel advances in pancreatic cancer treatment. Expert Rev Anticancer Ther 8 : 993 1002.
29. Wakimoto N, Yin D, O'Kelly J, Haritunians T, Karlan B, Said J et al 2008). Cucurbitacin B has a potent antiproliferative effect on breast cancer cells in vitro and in vivo. Cancer Sci 99 : 1793 1797.
30. Wallace JA, Locker G, Nattam S, Kasza K, Wade-Oliver K, Vokes EE et al 2007). Sorafenib (S) plus gemcitabine (G) for advanced pancreatic cancer (PC): a phase II trial of the University of Chicago Phase II Consortium. J Clin Oncol 2007 ASCO Annual Meeting Proc Part I 25: 4608.
31. Yin D, Wakimoto N, Xing H, Lu D, Huynh T, Wang X et al 2008). Cucurbitacin B markedly inhibits growth and rapidly affects the cytoskeleton in glioblastoma multiforme. Int J Cancer 123 : 1364 1375.
32. Young GA, Croaker G, Vincent PC, Forrest P, Morris TC (1987). The CFU-C assay in patients with neutropenia and, in particular, drug associated neutropenia. Clin Lab Haematol 9 : 245 253.
33. Zervos AS, Gyuris J, Brent R (1993). Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell 72 : 223 232.