Synergistic effect of mTOR inhibitor rapamycin and fluorouracil in inducing apoptosis and cell senescence in hepatocarcinoma cells

Cancer Biology and Therapy

Volumn 7, Issue 3, 2008, Pages 392-396

  Bu, Xinxin ^a   Le, Chen ^b   Jia, Fengqi ^a   Guo, Xianling ^a   Zhang, Li ^a   Zhang, Baihe ^a   Wu, Mengchao ^a   Wei, Lixin ^a  

^a Eastern Hepatobiliary Hospital   (China)

^b SECOND MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

Apoptosis; Cell senescence; Chemotherapy; Hepatocarcinoma; mTOR; Rapamycin

Indexed keywords

FLUOROURACIL; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; RAPAMYCIN; TRANSCRIPTION FACTOR AP 1;

APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CARCINOGENESIS; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CELL DIFFERENTIATION; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; DRUG POTENTIATION; ENZYME ACTIVITY; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; PROTEIN FUNCTION; SENESCENCE; SIGNAL TRANSDUCTION;

EID: 45349106007     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.7.3.5366     Document Type: Article

References (41)

1. El-Serag HB. Hepatocellular carcinoma: An epidemiologic view. J Clin Gastroenterol 2002; 35:S72-8.
2. Roberts LR, Gores GJ. Hepatocellular carcinoma: Molecular pathways and new therapeutic targets. Semin Liver Dis 2005; 25:212-25.
3. Blume-Jensen P, Hunter T. Oncogenic kinase signaling. Nature (Lond.) 2001; 411:355-65.
4. Datta SR, Brunet A, Greenberg ME. Cellular survival: A play in three Akts. Genes Dev 1999; 13:2905-27.
5. Brown EJ, Albers MW, Shin TB, Ocjlawa K, Keith CT, Lane WS, Schreiber SL. A mammalian protein targeted by G1-arresting rapamycin receptor complex. Nature(Lond.) 1994; 369:756-8.
6. Chiu MI, Katz H, Berlin V. RAPT1, a mammalian homolog of yeast TOR, interact with the FKBP/ rapamycin complex. Proc Natl Acad Sci 1994; 91:12574-8.
7. Sabatini DM, Erdjument-Bromage H, Liu M, Tempst P, Snyder SH. RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 1994; 78:35-43.
8. Brown EJ, Beal PA, keith CT, Chen J, Shin TB, Schreiber SL. Control of p70s6 kinase activity of FRAP in vivo. Nature 1995; 377:441-6.
9. Burnett PE, Barrow RK, Cohen NA, Snyder SH, Sabatini DM. RAFT1 phosphorylation of the translational regulators p70s6 kinase and 4E-BP1. Proc Natl Acad Sci 1998; 95:1432-7.
10. Isotani S, Hara K, Tokunaga C, Inoue H, Avruch J, Yonezawa K. Immunopurified mammalian target of rapamycin phosphorylates and activates p70 S6 kinase alpha in vitro. J Biol Chem 1999; 274:34493-8.
11. Eguchi S, Tokunaga C, Hidayat S, Oshiro N, Yoshino K, Kikkawa U, Yonezawa K. Different roles for the TOS and RAIP motifs of the translational regulator protein 4E-BP1 in the association with raptor and phosphorylation by mTOR in the regulation of cell size. Genes Cells 2006; 11:757-66.
12. Kuntebommanahalli NT, John E, Huang S, Karen AV, Glen SG, Franklin CH, Peter JH. Insulin-like growth factor □-mediated protein from rapamycin -induced apoptosis is dependent of Ras-Erk1-Erk2 and phosphatidylinositol3′ -kinase-Akt signaling pathway. Cancer Res 2003; 63:364-74.
13. Shi Y, Frankel A, Radvanyi LG, Penn LZ, Miller RG, Mills GB. Rapamycin enhances apoptosis and increases sensitivity to cisplatin in vitro. Cancer Res 1995; 55:1982-8.
14. Terada N, Patel HR, Takase K, Kohno K, Nairn AC, Gelfand EW. Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins. Proc Natl Acad Sci 1994; 91:11477-81.
15. Nielsen FC, Ostergaard L, Nielsen J, Christiansen J. Growth-dependent translation of IGF-II mRNA by a rapamycin-sensitive pathway. Nature (Lond.) 1995; 377:358-62.
16. Rosenwald IB, Kaspar R, Rousseau D, Gehrke L, Lebulch P, Chen JJ, Schmidt EV, Sonenberg N, London IM. Eukaryotic translation initiation factor 4E regulates expression of cyclin D1 at transcriptional and post -transcriptional levels. J Biol Chem 1995; 270:21176-280.
17. Castedo M, Ferri KF, Kroemer G. Mammalian target of rapamycin (mTOR): Pro- and anti-apoptotic. Cell Death Differ 2002; 9:99-100.
18. Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res 1961; 25:585-621.
19. Handa JT, Murad S, Jaffe GJ. Minoxidil inhibits ocular cell proliferation and lysyl hydroxylase activity. Invest Ophthalmol Vis Sci 1993; 34:567-75.
20. Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, Stein H, Dorken B, Jenuwein T, Schmitt CA. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 2005; 436:660-5.
21. Huang C, Ma WY, Ryan CA, Dong Z. Proteinase inhibitors I and II from potatoes specifically block UV-induced activator protein-1 activation through a pathway that is independent of extracellular signal-regulated kinases, c-Jun N-terminalkinases, and P38 kinase. Proc Natl Acad Sci 1997; 94:11957-62.
22. Huang C, Ma WY, Hecht SS, Dong Z. Inositol hexaphosphate inhibits cell transformation and activator protein 1 activation by targeting phosphatidylinositol-3 kinase. Cancer Res 1997; 57:2873-8.
23. Pietra G, Pietra R, Mortarini G, Parmiani, Anichini A. Phases of apoptosis of melanoma cells, but not of normal melanocytes, differently affect maturation of myeloid dendritic cells. Cancer Res 2001; 61:8218-26.
24. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci 1995; 92:9363-7.
25. Greten TF, Blum HE, Manns MP, Geissler M. Treatment of hepatocellular carcinoma. Z Gastroenterol 2006; 44:43-9.
26. Muller C. Hepatocellular carcinoma - rising incidence, changing therapeutic strategies. Wien Med Wochenschr 2006; 156:404-9.
27. Abraham RT. Identification of TOR signaling complexes: More TORC for the cell growth engine. Cell 2002; 11:9-12.
28. Erbay E, Chen J. The mammalian target of rapamycin regulates C2C12 myogenesis via a kinase-independent mechanism. J Biol Chem 2002; 276:36079-82.
29. Shu L, Zhang X, Houghton PJ. Myogenic differentiation is dependent on both the kinase function and the N-terminal sequence of mammalian target of rapamycin. J Biol Chem 2002; 277:16726-32.
30. Jacinto E, Hall MN. Tor signalling in bugs, brain and brawn. Nat Rev Mol Cell Biol 2003; 4:117-26.
31. Braun-Dullaeus RC, Mann MJ, Seay U, Zhang L, von Der Leyen HE, Morris RE, Dzau VJ. Cell cycle protein expression in vascular smooth muscle cells in vitro and in vivo is regulated through phosphatidylinositol 3-kinase and mammalian target of rapamycin. Arterioscler Thromb Vasc Biol 2001; 21:1152-8.
32. Guba M, von Breitenbuch P, Steinbauer M, Koehl G, Flegel S, Hornung M, Bruns CJ, Zuelke C, Farkas S, Anthuber M. Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: Involvement of vascular endothelial growth factor. Nat Med 2002; 8:128-35.
33. Choi JH, Bertram PG, Drenan R, Carvalho J, Zhou HH, Zheng XF. The FKBP12-rapam ycin-associated protein (FRAP) is a CLIP-170 kinase. EMBO 2002; 3:988-94.
34. Houghton PJ, Huang S. mTOR as a target for cancer therapy. Curr TopMicrobiol Immunol 2004; 279:339-59.
35. Gingras AC, Raught B, Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev 2002; 15:807-26.
36. Huang S, Houghton PJ. Inhibitors of mammalian target of rapamycin as novel antitumor agents: From bench to clinic. Curr Opin Investig Drugs 2002; 3:295-304.
37. Bringold F, Serrano M. Tumor suppressors and oncogenes in cellular senescence. Exp Gerontol 2000; 35:317-29.
38. Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, et al. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell 1987; 49:729-39.
39. Manna SK, Aggarwal BB. Wortmannin inhibits activation of nuclear transcription factors NF-κB and activated protein-1 induced by lipopolysaccharide and phorbol ester. FEBS Lett 2000; 473:113-8.
40. Baldwin A. The NF-κB and IkB proteins: New discoveries and insights. Annu Rev Immunol 1996; 14:649-83.
41. Gilmore TD, Koedood M, Piffat KA, White DW. Rel/NF-κB/IκB proteins and cancer. Oncogene1996; 13:1367-78.