Cucurbitacin: Ancient compound shedding new light on cancer treatment

TheScientificWorldJournal

Volumn 10, Issue , 2010, Pages 413-418

  Lee, Dhong Hyun ^a,b   Iwanski, Gabriela B ^a   Thoennissen, Nils H ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Cancer; Chemotherapy; Cucurbitacin; Doxorubicin; ERK inhibitor; Gemcitabine; JAK STAT pathway; MAPK pathway; STAT3 inhibitor; Synergism

Indexed keywords

CUCURBITACIN; CUCURBITACIN B; CUCURBITACIN E; CYCLIN A; CYCLIN B1; CYCLIN DEPENDENT KINASE 1; CYCLIN E; CYCLOOXYGENASE 2; DOXORUBICIN; F ACTIN; G ACTIN; GEMCITABINE; I KAPPA B KINASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; JANUS KINASE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; PROTEIN KINASE B; PROTEIN P21; REACTIVE OXYGEN METABOLITE; STAT PROTEIN; STAT3 PROTEIN; UNCLASSIFIED DRUG; VIMENTIN;

ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER CELL; CANCER CELL CULTURE; CANCER CHEMOTHERAPY; CARCINOGENESIS; CELL CYCLE ARREST; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL PROLIFERATION; CELL SHAPE; CELL SURVIVAL; CUCUMBER; CYTOKINESIS; CYTOSKELETON; CYTOTOXICITY; DOWN REGULATION; DRUG EFFICACY; DRUG EXPOSURE; DRUG MECHANISM; DRUG MEGADOSE; DRUG POTENTIATION; DRUG PURIFICATION; DRUG SCREENING; HOMEOSTASIS; HUMAN; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; INTOXICATION; MICROENVIRONMENT; MICROTUBULE; MOMORDICA; MOMORDICA BALSAMINA; MULTINUCLEAR CELL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SHORT SURVEY; SIGNAL TRANSDUCTION; UPREGULATION;

ANTINEOPLASTIC AGENTS; CUCURBITACINS; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; MAP KINASE SIGNALING SYSTEM; NEOPLASMS; TRANSCRIPTION FACTORS;

EID: 77951723076     PISSN: None     EISSN: 1537744X     Source Type: Journal    
DOI: 10.1100/tsw.2010.44     Document Type: Short Survey

References (29)

1. Cragg, G.M. and Newman, D.J. (2004/Rev. 2006) Plants as a source of anti-cancer agents. In Ethnopharmacology. Elisabetsky, E. and Etkin, N.L., Eds. In Encyclopedia of Life Support Systems (EOLSS). Developed under the Auspices of the UNESCO. Eolss Publishers, Oxford,U.K. http://www.eolss.net
2. Pezzuto, J.M. (1997) Plant-derived anticancer agents. Biochem. Pharmacol. 53, 121-133.
3. Geissman, T.A. (1964) New substances of plant origin. Annu. Rev. Pharmacol. 4, 305-316.
4. Chen, J.C., Chiu, M.H., Nie, R.L., Cordell, G.A., and Qiu, S.X. (2005) Cucurbitacins and cucurbitane glycosides: structures and biological activities. Nat. Prod. Rep. 22, 386-399. (Pubitemid 40885718)
5. Metcalf, R.L. (1986) Coevolutionary adaptations of rootworm beetles (Coleoptera: Chrysomelidae) to cucurbitacins. J. Chem. Ecol. 12, 1109-1124.
6. Raikhlin-Eisenkraft, B. and Bentur, Y. (2000) Ecballium elaterium (squirting cucumber) - remedy or poison? Clin. Toxicol. 38, 305-308.
7. Shoemaker, R.H. (2006) The NCI60 human tumor cell line anticancer drug screen. Nat. Rev. Cancer 10, 813-823.
8. Yu, H. and Jove, R. (2004) The stats of cancer - new molecular targets come to age. Nat. Rev. Cancer 4, 97-105. (Pubitemid 38198738)
9. Musza, L.L., Speight, P., McElhiney, S., Barrow, C.J., Gillum, A.M., Cooper, R., and Killar, L.M. (1994) Cucurbitacins, cell adhesion inhibitors from Conobea scoparioides. J. Nat. Prod. 57, 1498-1502.
10. Duncan, K.L., Duncan, M.D., Alley, M.C., and Sausville, E.A. (1996) Cucurbitacin E-induced disruption of the actin and vimentin cytoskeleton in prostate carcinoma cells. Biochem. Pharmacol. 52, 1553-1560.
11. Haritunians, T., Gueller, S., Zhang, L., Badr, R., Yin, D., Xing, H., Fung, M.C., and Koeffler, H.P. (2008) Cucurbitacin B induces differentiation, cell cycle arrest, and actin cytoskeletal alterations in myeloid leukemia cells. Leuk. Res. 32, 1366-1373.
12. Wakimoto, N., Yin, D., O'Kelly, J., Haritunians, T., Karlan, B., Said, J., Xing, H., and Koeffler, H.P. (2008) Cucurbitacin B has a potent antiproliferative effect on breast cancer cells in vitro and in vivo. Cancer Sci. 99, 793-1797.
13. Yin, D., Wakimoto, N., Xing, H., Lu, D., Huynh, T., Wang, X., Black, K.L., and Koeffler, H.P. (2008) Cucurbitacin B markedly inhibits growth and rapidly affects the cytoskeleton in glioblastoma multiforme. Int. J. Cancer 123, 1364-1375.
14. Thoennissen, N.H., Iwanski, G.B., Doan, N.B., Okamoto, R., Lin, P., Abbassi, S., Song, J.H., Yin, D., Toh, M., Xie, W.D., Said, J.W., and Koeffler, H.P. (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.
15. Tannin-Spitz, T., Grossman, S., Dovrat, S., Gottlieb, H.E., and Bergman M. (2007) Growth inhibitory activity of cucurbitacin glucosides isolated from Citrullus colocynthis on human breast cancer cells. Biochem. Pharmacol. 73, 56-67. (Pubitemid 44853933)
16. Blaskovich, M.A., Sun, J., Cantor, A., Turkson, J., Jove, R., and Sebti, S.M. (2003) 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. 63, 1270-1279. (Pubitemid 36348705)
17. Sun, J., Blaskovich, M.A., Jove, R., Livingston, S.K., Coppola, D., and Sebti, S.M. (2006) Cucurbitacin Q: a selective STAT3 activation inhibitor with potent antitumor activity. Oncogene 24, 3236-3245. (Pubitemid 40695105)
18. Su, Y., Li, G., Zhang, X., Gu, J., Zhang, C., Tian, Z., and Zhang, J. (2008) JSI-124 inhibits glioblastoma multiforme cell proliferation through G(2)/M cell cycle arrest and apoptosis augment. Cancer Biol. Ther. 7, 1243-1249.
19. van Kester, M.S., Out-Luiting, J.J., von dem Borne, P.A., Willemze, R., Tensen, C.P., and Vermeer, M.H. (2008) Cucurbitacin I inhibits Stat3 and induces apoptosis in Sézary cells. J. Invest. Dermatol. 128, 1691-1695.
20. Shi X., Franko B., Frantz C., Amin H.M., and Lai, R. (2006) JSI-124 (cucurbitacin I) inhibits Janus kinase-3/signal transducer and activator of transcription-3 signalling, downregulates nucleophosmin-anaplastic lymphoma kinase (ALK), and induces apoptosis in ALK-positive anaplastic large cell lymphoma cells. Br. J. Haematol. 135, 26-32. (Pubitemid 44337660)
21. Lin W. and Karin M. (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J. Clin. Invest. 117, 1175-1183. (Pubitemid 46718402)
22. Jayaprakasam, B., Seeram, N.P., and Nair, M.G. (2003) Anticancer and antiinflammatory activities of cucurbitacins from Cucurbita andreana. Cancer Lett. 189, 11-16. (Pubitemid 35351514)
23. Park, C.S., Lim, K.J., Baek, S.H., Sohn, H.O., Lee, D.W., Yun, H.Y., Baek, K.J., Lee, H.S., and Kwon, N.S. (2004) Inhibition of nitric oxide generation by 23,24-dihydrocucurbitacin D in mouse peritoneal macrophages. J. Pharmacol. Exp. Ther. 309, 705-710. (Pubitemid 38542626)
24. Escandell, J.M., Recio, M.C., Máñez, S., Giner, R.M., Cerdá-Nicolás, M., and Ríos, J.L. (2007) Cucurbitacin R reduces the inflammation and bone damage associated with adjuvant arthritis in lewis rats by suppression of tumor necrosis factor-alpha in T lymphocytes and macrophages. J. Pharmacol. Exp. Ther. 320, 581-590.
25. Escandell, J.M., Kaler, P., Recio, M.C., Sasazuki, T., Shirasawa, S., Augenlicht, L., Ríos, J.L., and Klampfer, L. (2008) Activated kRas protects colon cancer cells from cucurbitacin-induced apoptosis: the role of p53 and p21. Biochem. Pharmacol. 76, 198-207.
26. Chan, K.T., Li, K., Liu, S.L., Chu, K.H., Toh, M., and Xie W.D. (2009) Cucurbitacin B inhibits STAT3 and the Raf/MEK/ERK pathway in leukemia cell line K562. Cancer Lett. 289(1), 46-52.
27. Takahashi. N., Yoshida, Y., Sugiura, T., Matsuno, K., Fujino, A., and Yamashita, U. (2009) Cucurbitacin D isolated from Trichosanthes kirilowii induces apoptosis in human hepatocellular carcinoma cells in vitro. Int. Immunopharmacol. 9, 508-513.
28. Sadzuka, Y., Hatakeyama, H., Daimon, T., and Sonobe, T. (2008) Screening of biochemical modulator by tumor cell permeability of doxorubicin. Int. J. Pharm. 354, 63-69. (Pubitemid 351400329)
29. Ramalhete, C., Molnár, J., Mulhovo, S., Rosário, V.E., and Ferreira, M.J. (2009) New potent P-glycoprotein modulators with the cucurbitane scaffold and their synergistic interaction with doxorubicin on resistant cancer cells. Bioorg. Med. Chem. 17, 6942-6951.