Cucurbitacin B induces apoptosis by inhibition of the JAK/STAT pathway and potentiates antiproliferative effects of gemcitabine on pancreatic cancer cells

Cancer Research

Volumn 69, Issue 14, 2009, Pages 5876-5884

  Thoennissen, Nils H ^a   Iwanski, Gabriela B ^a   Doan, Ngan B ^b   Okamoto, Ryoko ^a   Lin, Patricia ^a   Abbassi, Sam ^a   Jee, Hoon Song ^a   Yin, Dong ^a   Toh, Melvin ^c   Wei, Dong Xie ^c   Said, Jonathan W ^b   Koeffler, H Phillip ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b Santa Monica UCLA Medical Center   (United States)

^c (Holdings) Inc   (Hong Kong)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; CASPASE 9; CUCURBITACIN; CUCURBITACIN B; CYCLIN A; CYCLIN B1; CYCLIN DEPENDENT KINASE INHIBITOR 1; GEMCITABINE; JANUS KINASE 2; PROTEIN BCL XL; PROTEIN P53; STAT3 PROTEIN; STAT5 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER GROWTH; CELL CYCLE ARREST; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL PROLIFERATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG POTENTIATION; DRUG SAFETY; ENZYME INHIBITION; FEMALE; GENE EXPRESSION; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; TUMOR VOLUME; TUMOR XENOGRAFT; UPREGULATION;

ANIMALS; ANTIMETABOLITES, ANTINEOPLASTIC; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; BLOTTING, WESTERN; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; DEOXYCYTIDINE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SYNERGISM; FEMALE; FLOW CYTOMETRY; GIANT CELLS; HUMANS; JANUS KINASES; MICE; MOLECULAR STRUCTURE; PANCREATIC NEOPLASMS; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS; TIME FACTORS; TRITERPENES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 67650995911     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-09-0536     Document Type: Article

References (37)

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006;56:106-30.
2. Vulfovich M, Rocha-Lima C. Novel advances in pancreatic cancer treatment. Expert Rev Anticancer Ther 2008;8:993-1002.
3. Sun J, Blaskovich MA, Jove R, Livingston SK, Coppola D, Sebti SM. Cucurbitacin Q: a selective STAT3 activation inhibitor with potent antitumor activity. Oncogene 2005;24:3236-45.
4. Toyonaga T, Nakano K, Nagano M, et al. Blockade of constitutively activated Janus kinase/signal transducer and activator of transcription-3 pathway inhibits growth of human pancreatic cancer. Cancer Lett 2003;201:107-16.
5. Sahu RP, Srivastava SK. The role of STAT-3 in the induction of apoptosis in pancreatic cancer cells by benzyl isothiocyanate. J Natl Cancer Inst 2009 Jan 27. Epub ahead of print.
6. Wakimoto N, Yin D, O'Kelly J, et al. Cucurbitacin B has a potent antiproliferative effect on breast cancer cells in vitro and in vivo. Cancer Sci 2008;99:1793-7.
7. Yin D, Wakimoto N, Xing H, et al. Cucurbitacin B markedly inhibits growth and rapidly affects the cytoskeleton in glioblastoma multiforme. Int J Cancer 2008;123:1364-75.
8. Haritunians T, Gueller S, Zhang L, et al. Cucurbitacin B induces differentiation, cell cycle arrest, and actin cytoskeletal alterations in myeloid leukemia cells. Leuk Res 2008;32:1366-73.
9. 2: antitumor activity against leukemia, myeloma, and colon cancer cells. J Natl Cancer Inst 2003;95:896-905.
10. 3 analogs: a unique class of potent inhibitors of proliferation of prostate, breast, and hematopoietic cancer cells. Cancer Res 1998;58:3370-5.
11. Luong QT, O'Kelly J, Braunstein GD, Hershman JM, Koeffler HP. Antitumor activity of suberoylanilide hydroxamic acid against thyroid cancer cell lines in vitro and in vivo. Clin Cancer Res 2006;12:5570-7.
12. Sun FX, Tohgo A, Bouvet M, et al. Efficacy of camptothecin analog DX-8951f (exatecan mesylate) on human pancreatic cancer in an orthotopic metastatic model. Cancer Res 2003;63:80-5.
13. Solit DB, Zheng FF, Drobnjak M, et al. 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 2002;8:986-93.
14. Chou TC, Hayball MP. CalcuSyn: Windows software for dose effects analysis [manual]. Montana: Biosoft; 1996. p. 1-56.
15. Chou TC, Talalay P. Quantitative analysis of doseeffect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22: 27-55.
16. Turkson J, Bowman T, Garcia R, et al. Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol Cell Biol 1998; 18:2545-52.
17. Li WX. Canonical and non-canonical JAK-STAT signaling. Trends Cell Biol 2008;18:545-51.
18. Gartel AL, Tyner AL. The role of the cyclin-dependent kinase inhibitor p21 in apoptosis. Mol Cancer Ther 2002; 1:639-49.
19. Burris HA III, Moore MJ, Andersen J. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15:2403-13.
20. Moore MJ, Goldstein D, Hamm J, et al. 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 2007;25:1960-6.
21. Kindler HL, Niedzwiecki D, Hollis D, et al. A doubleblind, 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 GroupB (CALGB). J Clin Oncol 2007 ASCO Annu Meet Proc Part I, Vol. 25, No. 18S ( Jun 20 Suppl), p. 4508.
22. Wallace JA, Locker G, Nattam S, et al. 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 Annu Meet Proc Part I, Vol. 25, No. 18S ( Jun 20 Suppl), p. 4608.
23. Oettle H, Pelzer U, Stieler J, et al. Oxaliplatin/folinic acid/5-fluorouracil [24h] (OFF) plus best supportive care versus best supportive care alone (BSC) in second-line therapy of gemcitabine-refractory advanced pancreatic cancer (CONKO 003). J Clin Oncol 2005 ASCO Annu Meet Proc (Post-Meet Ed) Vol. 23, No. 16S, Part I of II ( Jun 1 Suppl), p. 4031.
24. Mitry E, Ducreux M, Ould-Kaci M, et al. Oxaliplatin combined with 5-FU in second line treatment of advanced pancreatic adenocarcinoma. Results of a phase II trial. Gastroenterol Clin Biol 2006;30:357-63.
25. Tan SH, Nevalainen MT. Signal transducer and activator of transcription 5A/B in prostate and breast cancers. Endocr Relat Cancer 2008;15:367-90.
26. Lewis RS, Ward AC. Stat5 as a diagnostic marker for leukemia. Expert Rev Mol Diagn 2008;8:73-82.
27. Adnane J, Bizouarn FA, Qian Y, Hamilton AD, Sebti SM. p21(WAF1/CIP1) is upregulated by the geranylger-anyltransferase I inhibitor GGTI-298 through a transforming growth factor β- and Sp1-responsive element: involvement of the small GTPase RhoA. Mol Cell Biol 1998;18:6962-70.
28. Yamaguchi Y, Watanabe H, Yrdiran S, et al. Detection of mutations of p53 tumor suppressor gene in pancreatic juice and its application to diagnosis of patients with pancreatic cancer: comparison with K-ras mutation. Clin Cancer Res 1999;5:1147-53.
29. Datto MB, Li Y, Panus JF, Howe DJ, Xiong Y, Wang XF. Transforming growth factor h induces the cyclindependent kinase inhibitor p21 through a p53-independent mechanism. Proc Natl Acad Sci U S A 1995;92:5545-9.
30. WAF1/CIP1/SDI1 is elevated through a p53-independent pathway by mimosine. Cell Growth Differ 1996;7:893-1.
31. WAF1/CIP1 expression by p53-independent pathways. Oncogene 1996;12:1557-64.
32. Steinman RA, Hoffman B, Iro A, Guillouf C, Liebermann DA, el-Houseini ME. Induction of p21 (WAF-1/CIP1) during differentiation. Oncogene 1994;9: 3389-96.
33. Bai J, Sui J, Demirjian A, Vollmer CM, Jr., Marasco W, Callery MP. Predominant Bcl-XL knockdown disables antiapoptotic mechanisms: tumor necrosis factor-related apoptosis-inducing ligand-based triple chemotherapy overcomes chemoresistance in pancreatic cancer cells in vitro. Cancer Res 2005;65:2344-52.
34. Ghaneh P, Kawesha A, Evans JD, Neoptolemos JP. Molecular prognostic markers in pancreatic cancer. J Hepatobiliary Pancreat Surg 2002;9:1-11.
35. Catlett-Falcone R, Dalton WS, Jove R. STAT proteins as novel targets for cancer therapy. Signal transducer an activator of transcription. Curr Opin Oncol 1999;11: 490-6.
36. Alas S, Bonavida B. Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin's lymphoma and multiple myeloma to chemotherapeutic drugmediated apoptosis. Clin Cancer Res 2003;9:316-26.
37. Blaskovich MA, Sun J, Cantor A, Turkson J, Jove R, Sebti SM. Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice. Cancer Res 2003;63:1270-9.