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6.5. References

  1. R. Ockner, N. Lysenko, N. Wu, and N. Bass, Hepatocyte growth inhibitors modulate mitochondrial and extramitochondrial fatty acid oxidation, Hepatology 24:253A (Abstract) (1996).

    Google Scholar 

  2. M. Bugaut, and M. Bentéjac, Biological effects of short-chain fatty acids in nonruminant mammals., Annu Rev Nutr 13:217–241 (1993).

    Article  CAS  PubMed  Google Scholar 

  3. A. Toscani, D. Soprano, and K. Soprano, Molecular analysis of sodium butyrateinduced growth arrest, Oncogene Res 3:223–238 (1988).

    CAS  PubMed  Google Scholar 

  4. A. Hague, A. Manning, K. Hanlon, L. Huschtscha, D. Hart, and C. Paraskeva, Sodium butyrate induces apoptosis in human colonic tumour cell lines in a p53-independent pathway: implications for the possible role of dietary fibre in the prevention of largebowel cancer, Intl J Cancer 55:498–505 (1993).

    CAS  Google Scholar 

  5. R. Gope, and M. Gope, Effect of sodium butyrate on the expression of retinoblastoma (RB1) and P53 gene and phosphorylation of retinoblastoma protein in human colon tumor cell line HT29, Cell Mol Biol 39:589–597 (1993).

    CAS  PubMed  Google Scholar 

  6. D. Heruth, G. Zirnstein, J. Bradley, and P. Rothberg, Sodium butyrate causes an increase in the block to transcriptional elongation in the c-myc gene in SW837 rectal carcinoma cells, J Biol Chem 268:20466–20472 (1993).

    CAS  PubMed  Google Scholar 

  7. C. Vaziri, L. Slice, and D. Faller, Butyrate-induced G1 arrest results from p21-independent disruption of retinoblastoma protein-mediated signals, Cell Growth Differentiation 9:465–474 (1998).

    CAS  PubMed  Google Scholar 

  8. M. Barshishat, S. Polak-Charcon, and B. Schwartz, Butyrate regulates E-cadherin transcription, isoform expression and intracellular position in colon cancer cells., Br J Cancer 82:195–203 (2000).

    CAS  PubMed  Google Scholar 

  9. K. Nakano, T. Mizuno, Y. Sowa, et al., Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line, J Biol Chem 272:22199–22206 (1997).

    CAS  PubMed  Google Scholar 

  10. S. Archer, S. Meng, A. Shei, and R. Hodin, p21WAF1 is required for butyrate-mediated growth inhibition of human colon cancer cells., Proc Natl Acad Sci USA 95:6791–6796 (1998).

    Article  CAS  PubMed  Google Scholar 

  11. B. Heerdt, M. Houston, G. Anthony, and L. Augenlicht, Mitochondrial membrane potential DYm in the coordination of p53-independent proliferation and apoptosis pathways in human colonic carcinoma cells, Cancer Res 58:2869–2875 (1998).

    CAS  PubMed  Google Scholar 

  12. B. Schwartz, C. Avivi-Green, and S. Polak-Charcon, Sodium butyrate induces retinoblastoma protein dephosphorylation, p16 expression and growth arrest of colon cancer cells, Molec Cellular Biochem 188:21–30 (1998).

    CAS  Google Scholar 

  13. A. Wähtershäser, S. Loitsch, and J. Stein, PPAR-gamma is selectively upregulated in Caco-2 cells by butyrate, Biochem Biophys Res Comm 272:380–385 (2000).

    Google Scholar 

  14. J. McBain, A. Eastman, C. Nobel, and G. Mueller, Apoptotic death in adenocarcinoma cell lines induced by butyrate and other histone deacetylase inhibitors, Biochem Pharmacol 53:1357–1368 (1997).

    Article  CAS  PubMed  Google Scholar 

  15. P. Garland, E. Newsholme, and P. Randle, Regulation of glucose uptake by muscle: Effects of fatty acids and ketone bodies, and of alloxan-diabetes and starvation, on pyruvate metabolism and on lactate/pyruvate and L-glycerol 3-phosphate/dihydroxyacetone phosphate concentration ratios in rat heart and rat diaphragm muscles., Biochem J 93:665–678 (1964).

    CAS  PubMed  Google Scholar 

  16. T._A. Hopkins, M. C. Sugden, M. J. Holness, R. Kozak, J. R. Dyck, and G. D. Lopaschuk, Control of cardiac pyruvate dehydrogenase activity in peroxisome proliferator-activated receptor-alpha transgenic mice, Am J Physiol Heart Circ Physiol 285:H270–6 (2003).

    CAS  PubMed  Google Scholar 

  17. L. Wojtczak, and P. Schöfeld, Effect of fatty acids on energy coupling processes in mitochondria, Biochim Biophys Acta 1183:41–57 (1993).

    CAS  PubMed  Google Scholar 

  18. L. Svensson, S. Kilpelänen, J. Hiltunen, and S. Alexson, Characterization and isolation of enzymes that hydrolyze short-chain acyl-CoA in rat-liver mitochondria, Eur J Biochem 239:526–531 (1996).

    Article  CAS  PubMed  Google Scholar 

  19. J. Amatruda, S. Margolis, and D. Lockwood, Regulation of ketone body production from [14C]palmitate in rat liver mitochondria: effects of cyclic nucleotides and unlabeled fatty acids., Biochem Biophys Res Commun 67:1337–1345 (1975).

    Article  CAS  PubMed  Google Scholar 

  20. I. Reynolds, and T. Hastings, Glutamate induces the production of reactive oxygen species in cultured forebrain neurons following NMDA receptor activation, J Neurosci 15:3318–3327 (1995).

    CAS  PubMed  Google Scholar 

  21. V. Skulachev, Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants, Quart Rev Biophys 29:169–202 (1996).

    CAS  Google Scholar 

  22. A. Nègre-Salvayre, C. Hirtz, G. Carrera, et al., A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation, FASEB J 11:80–815 (1997).

    Google Scholar 

  23. A. Stout, H. Raphael, B. Kanterewicz, E. Klann, and I. Reynolds, Glutamate-induced neuron death requires mitochondrial calcium uptake, Nature Neurosci 1:366–373 (1998).

    CAS  PubMed  Google Scholar 

  24. S. Korshunov, O. Kokina, E. Ruuge, V. Skulachev, and A. Starkov, Fatty acids as natural uncouplers preventing generation of O2-and H2O2 by mitochondria in the resting state, FEBS Letts 435:215–218 (1998).

    Article  CAS  Google Scholar 

  25. P. Oliveira, A. Rolo, V. Sardã, P. Coxito, C. Palmeira, and A. Moreno, Carvedilol in heart mitochondria protonophore or opener of the mitochondrial KATP channels?, Life Sci 69:123–132 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. M. Tisdale, Role of acetoacetyl-CoA synthetase in acetoacetate utilization by tumor cells, Cancer Biochem Biophys 7:101–107 (1984).

    CAS  PubMed  Google Scholar 

  27. S. Beck, and M. Tisdale, Effect of insulin on weight loss and tumour growth in a cachexia model., Br J Cancer 59:677–681 (1989).

    CAS  PubMed  Google Scholar 

  28. W. Zhang, S. Churchill, R. Lindahl, and P. Churchill, Regulation of D-betahydroxybutyrate dehydrogenase in rat hepatoma cell lines, Cancer Res 49:2433–2437 (1989).

    CAS  PubMed  Google Scholar 

  29. M. Mandal, X. Wu, and R. Kumar, Bcl-2 deregulation leads to inhibition of sodium butyrate-induced apoptosis in human colorectal carcinoma cells, Carcinogenesis 18:229–232 (1997).

    Article  CAS  PubMed  Google Scholar 

  30. Y. Fan, J. Zhang, R. Barhoumi, et al., Antagonism of CD95 signaling blocks butyrate induction of apoptosis in young adult mouse colonic cells., Am J Physiol 277:C310–C319 (1999).

    CAS  PubMed  Google Scholar 

  31. M. Alam, T. Midtvedt, and A. Uribe, Differential cell kinetics in the ileum and colon of germfree rats., Scand J Gastroenterol 29:445–451 (1994).

    CAS  PubMed  Google Scholar 

  32. C. Cherbuy, D.-V. B, M. M, and P. J, P, Duée, Effect of germfree state on the capacities of isolated rat colonocytes to metabolize n-butyrate, glucose, and glutamine., Gastroenterol. 109: 1890–1899 (1995).

    CAS  Google Scholar 

  33. B. Singh, A. Halestrap, and C. Paraskeva, Butyrate can act as a stimulator of growth or inducer of apoptosis in human colonic epithelial cell lines depending on the presence of alternative energy sources, Carcinogenesis 18:1265–1270 (1997).

    CAS  PubMed  Google Scholar 

  34. O. Kan, S. Baldwin, and A. Whetton, Apoptosis is regulated by the rate of glucose transport in an interleukin 3 dependent cell line, J Exp Med 180:917–923 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. Z. Kovacevic, and J. Mcgivan, Mitochondrial metabolism of glutamine and glutamate and its physiological significance, Physiol Rev 63:547–605 (1983).

    CAS  PubMed  Google Scholar 

  36. R. Nakashima, M. Paggi, and P. Pedersen, Contributions of glycolysis and oxidative phosphorylation to adenosine 5’-triphosphate production in AS-30D hepatoma cells. Cancer Res 44:5702–5706 (1984).

    CAS  PubMed  Google Scholar 

  37. M. Board, S. Humm, and E. Newsholme, Maximum activities of key enzymes of glycolysis, glutaminolysis, pentose phosphate pathway and tricarboxylic acid cycle in normal, neoplastic and suppressed cells., Biochem J 265:503–509 (1990).

    CAS  PubMed  Google Scholar 

  38. V. Goossens, J. Grooten, and W. Fiers, The oxidative metabolism of glutamine: A modulator of reactive oxygen intermediate-mediated cytotoxicity of tumor necrosis factor in L929 fibrosarcoma cells, J Biol Chem 271:192–196 (1996).

    CAS  PubMed  Google Scholar 

  39. K. Polyak, J. Kato, M. Solomon, et al., p27Kipl, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest, Genes Dev 8:9–22 (1994).

    CAS  PubMed  Google Scholar 

  40. C. Li, L. Suardet, and J. Little, Potential role of WAF1/Cip1/p21 as a mediator of TGF-beta cytoinhibitory effect, J Biol Chem 270:4971–4974 (1995).

    CAS  PubMed  Google Scholar 

  41. M. Datto, Y. Li, J. Panus, D. Howe, Y. Xiong, and X. Wang, Transforming growth factor beta induces the cyclin-dependent kinase inhibitor p21 through a p53-independent mechanism., Proc Natl Acad Sci USA 92:5545–5549 (1995).

    CAS  PubMed  Google Scholar 

  42. N. Muller, A. Reinacher-Schick, S. Baldus, et al., Smad4 induces the tumor suppressor E-cadherin and P-cadherin in colon carcinoma cells, Oncogene 21:6049–58 (2002).

    PubMed  Google Scholar 

  43. U. Kintscher, S. Wakino, D. Bruemmer, et al., TGF-beta(1) induces peroxisome proliferator-activated receptor gammal and gamma2 expression in human THP-1 monocytes, Biochem Biophys Res Commun 297:794–9 (2002).

    Article  CAS  PubMed  Google Scholar 

  44. A. Pellacani, P. Wiesel, S. Razavi, et al., Down-regulation of high mobility group-I(Y) protein contributes to the inhibition of nitric-oxide synthase 2 by transforming growth factor-beta1, J Biol Chem 276:1653–1659 (2001).

    Article  CAS  PubMed  Google Scholar 

  45. B. Gumbiner, Carcinogenesis: a balance between beta-catenin and APC, Current Biol 7:R443–R446 (1997).

    CAS  Google Scholar 

  46. A. Yap, W. Brieher, and B. Gumbiner, Molecular and functional analysis of cadherinbased adherens junctions, Ann Rev Cell Dev Biol 13:119–146 (1997).

    CAS  Google Scholar 

  47. J. Francis, C. Heyworth, E. Spooncer, A. Pierce, T. Dexter, and A. Whetton, Transforming growth factor-beta 1 induces apoptosis independently of p53 and selectively reduces expression of Bcl-2 in multipotent hematopoietic cells., J Biol Chem 275:39137–39145 (2000).

    Article  CAS  PubMed  Google Scholar 

  48. B. Herrera, M. Fernandez, A. Alvarez, et al.. Activation of caspases occurs downstream from radical oxygen species production, Bcl-xL down-regulation, and early cytochrome C release in apoptosis induced by transforming growth factor beta in rat fetal hepatocytes, Hepatology 34:548–56 (2001A).

    Article  CAS  PubMed  Google Scholar 

  49. B. Kim, M. Mamura, K. Choi, B. Calabretta, and S. Kim, Transforming growth factor beta 1 induces apoptosis through cleavage of BAD in a Smad3-dependent mechanism in FaO hepatoma cells, Mol Cell Biol 22:1369–1378 (2002).

    CAS  PubMed  Google Scholar 

  50. Y. Hong, H. Peng, F. La, and V. Liao, Hydrogen peroxide-mediated transcriptional induction of macrophage colony-stimulating factor by TGF-beta1, J Immun 159:2418–2423 (1997).

    CAS  PubMed  Google Scholar 

  51. B. Herrera, A. M. Alvarez, A. Sanchez, et al., Reactive oxygen species (ROS) mediates the mitochondrial-dependent apoptosis induced by transforming growth factor (beta) in fetal hepatocytes, Faseb J 15:741–51 (2001B).

    Article  CAS  PubMed  Google Scholar 

  52. G. Blobe, W. Schiemann, and H. Lodish, Role of transforming growth factor b in human disease., New Engl J Med 342:1350–1358 (2000).

    Article  CAS  PubMed  Google Scholar 

  53. R. Akhurst, and R. Derynck, TGF-beta signaling in cancer — a double-edged sword., Trends Cell Biol 11:S44–S51 (2001).

    CAS  PubMed  Google Scholar 

  54. L. Wakefield, and A. Roberts, TGF-beta signaling: positive and negative effects on tumorigenesis, Curr Opin Genet Dev 12:22–29 (2002).

    Article  CAS  PubMed  Google Scholar 

  55. Y. Shi, and J. Massague, Mechanisms of TGF-beta signaling from cell membrane to the nucleus, Cell 113:685–700 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. M. Cordenonsi, S. Dupont, S. Maretto, A. Insinga, C. Imbriano, and S. Piccolo, Links between tumor suppressors: p53 is required for TGF-beta gene responses by cooperating with Smads, Cell 113:301–14 (2003).

    Article  CAS  PubMed  Google Scholar 

  57. M. Miyazaki, R. Ohashi, T. Tsuji, K. Mihara, E. Gohda, and M. Namba, Transforming growth factor-beta 1 stimulates or inhibits cell growth via down-or up-regulation of p21/Waf1, Biochem Biophys Res Comm 246:873–880 (1998).

    CAS  PubMed  Google Scholar 

  58. A. Mauviel, K. Chung, A. Agarwal, K. Tamai, and J. Uitto, Cell-specific induction of distinct oncogenes of the Jun family is responsible for differential regulation of collagenase gene expression by transforming growth factor-beta in fibroblasts and keratinocytes, J Biol Chem 271:10917–10923 (1996).

    CAS  PubMed  Google Scholar 

  59. M. Azuma, K. Motegi, K. Aota, T. Yamashita, H. Yoshida, and M. Sato, TGF-beta1 inhibits NF-kappaB activity through induction of IkappaB-alpha expression in human salivary gland cells: a possible mechanism of growth suppression by TGF-betal., Exp Cell Res 250:213–222 (1999).

    Article  CAS  PubMed  Google Scholar 

  60. K. Matsuzaki, M. Date, F. Furukawa, et al., Regulatory mechanisms for transforming growth factor _ as an autocrine inhibitor in human hepatocellular carcinoma: implications for roles of smads in its growth, Hepatol 32:218–227 (2000).

    Article  CAS  Google Scholar 

  61. M. Macias-Silva, W. Li, J. I. Leu, M. A. Crissey, and R. Taub, Up-regulated transcriptional repressors SnoN and Ski bind Smad proteins to antagonize transforming growth factor-beta signals during liver regeneration, J Biol Chem 277:28483–90 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. M. Delcommenne, C. Tan, V. Gray, L. Rue, J. Woodgett, and S. Dedhar, Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase., Proc Natl Acad Sci USA 95:11211–11216 (1998).

    Article  CAS  PubMed  Google Scholar 

  63. Y. Li, J. Yang, C. Dai, C. Wu, and Y. Liu, Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis, J Clin Invest 112:503–16 (2003).

    Article  CAS  PubMed  Google Scholar 

  64. A. Bakin, A. Tomlinson, N. Bhowmick, H. Moses, and C. Arteaga, Phosphatidylinositol 3-kinase function is required for transforming growth factor bmediated epithelial to mesenchymal transition and cell migration., J Biol Chem 275:36803–36810 (2000).

    Article  CAS  PubMed  Google Scholar 

  65. F. Valdes, A. M. Alvarez, A. Locascio, et al., The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor beta in fetal rat hepatocytes, Mol Cancer Res 1:68–78 (2002).

    CAS  PubMed  Google Scholar 

  66. Y. Vodovotz, L. Chesler, H. Chong, et al., Regulation of transforming growth factor beta1 by nitric oxide, Cancer Res 59:2142–2149 (1999).

    CAS  PubMed  Google Scholar 

  67. Y. Vodovotz, C. Bogdan, J. Paik, Q. Xie, and C. Nathan, Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor beta, J Exp Med 178:605–613 (1993).

    Article  CAS  PubMed  Google Scholar 

  68. U. Heine, J. Burmester, K. Flanders, et al., Localization of transforming growth factor-beta 1 in mitochondria of murine heart and liver, Cell Regul 2:467–477 (1991).

    CAS  PubMed  Google Scholar 

  69. D. Anderson, C. Guerin, G. Hageman, B. Pfeffer, and K. Flanders, Distribution of transforming growth factor-beta isoforms in the mammalian retina., J Neurosci Res 42:63–79 (1995).

    Article  CAS  PubMed  Google Scholar 

  70. J. Potts, S. Bassnett, and D. Beebe, Expression of transforming growth factor beta in the embryonic avian lens coincides with the presence of mitochondria, Developmental Dynamics 203:317–323 (1995).

    CAS  PubMed  Google Scholar 

  71. S. Roth-Eichhorn, K. Kühl, and A. Gressner, Subcellular localization of (latent) transforming growth factor beta and the latent TGF-beta binding protein in rat hepatocytes and hepatic stellate cells, Hepatology 28:1588–1596 (1998).

    Article  CAS  PubMed  Google Scholar 

  72. W. Chen, W. Jin, H. Tian, et al., Requirement for transforming growth factor beta1 in controlling T cell apoptosis., J Exp Med 194:439–53 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. K. Flanders, N. Thompson, D. Cissel, et al., Transforming growth factor-beta 1: histochemical localization with antibodies to different epitopes., J Cell Biol 108:653–660 (1989).

    Article  CAS  PubMed  Google Scholar 

  74. S. Kim, A. Glick, M. Sporn, and A. Roberts, Characterization of the promoter region of the human transforming growth factor-beta 1 gene, J Biol Chem 264:402–408 (1989).

    CAS  PubMed  Google Scholar 

  75. T. Caver, F. O’Sullivan, L. Gold, and H. Gresham, Intracellular demonstration of active TGFbeta1 in B cells and plasma cells of autoimmune mice: IgG-Bound TGFbeta1 suppresses neutrophil function and host defense against staphylococcus aureus infection., J Clin Invest 98:2496–2506 (1996).

    CAS  PubMed  Google Scholar 

  76. B. Grasl-Kraupp, E. Schausberger, K. Hufnagl, et al., A novel mechanism for mitogenic signaling via pro-transforming growth factor alpha within hepatocyte nuclei, Hepatology 35:1372–80 (2002).

    Article  CAS  PubMed  Google Scholar 

  77. M. Joaquin, J. Rosa, C. Salvado, et al., Hepatocyte growth factor and transforming growth factor beta regulate 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene expression in rat hepatocyte primary cultures, Biochem J 314:235–240 (1996).

    CAS  PubMed  Google Scholar 

  78. G. Thoresen, and T. Christoffersen, Transforming growth factor beta 1 increases the phosphoenolpyruvate carboxykinase mRNA level in cultured rat hepatocytes, Cell Biol Intl 18:171–175 (1994).

    CAS  Google Scholar 

  79. H. Yamazaki, M. Arai, S. Matsumura, K. Inoue, and T. Fushiki, Intracranial administration of transforming growth factor-beta3 increases fat oxidation in rats, Am J Physiol Endocrinol Metab 283:E536–44 (2002).

    CAS  PubMed  Google Scholar 

  80. Y. Yamamura, X. Hua, S. Bergelson, and H. Lodish, Critical role of smads and AP-1 complex in transforming growth factor-b-dependent apoptosis, J Biol Chem 275:36295–36302 (2000).

    Article  CAS  PubMed  Google Scholar 

  81. I. Shin, A. V. Bakin, U. Rodeck, A. Brunet, and C. L. Arteaga, Transforming growth factor beta enhances epithelial cell survival via Akt-dependent regulation of FKHRL1, Mol Biol Cell 12:3328–39 (2001).

    CAS  PubMed  Google Scholar 

  82. C. Diez-Fernandez, D. Andres, and M. Cascales, Attenuating effects of heat shock against TGF-beta1-induced apoptosis in cultured rat hepatocytes, Free Radic Biol Med 33:835–46 (2002).

    CAS  PubMed  Google Scholar 

  83. C._M. Rodrigues, X. Ma, C. Linehan-Stieers, G. Fan, B. T. Kren, and C. J. Steer, Ursodeoxycholic acid prevents cytochrome c release in apoptosis by inhibiting mitochondrial membrane depolarization and channel formation, Cell Death Differ 6:842–54 (1999).

    Article  CAS  PubMed  Google Scholar 

  84. T. Y. Ling, Y. H. Huang, M. C. Lai, S. S. Huang, and J. S. Huang, Fatty acids modulate transforming growth factor-beta activity and plasma clearance, Faseb J 17:1559–61 (2003).

    CAS  PubMed  Google Scholar 

  85. F. N. Ziyadeh, B. B. Hoffman, D. C. Han, et al., Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice, Proc Natl Acad Sci U S A 97:8015–20 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. M. Fujimoto, Y. Maezawa, K. Yokote, et al., Mice lacking Smad3 are protected against streptozotocin-induced diabetic glomerulopathy, Biochem Biophys Res Commun 305:1002–7 (2003).

    Article  CAS  PubMed  Google Scholar 

  87. M. Isono, A. Mogyorosi, D. C. Han, B. B. Hoffman, and F. N. Ziyadeh, Stimulation of TGF-beta type II receptor by high glucose in mouse mesangial cells and in diabetic kidney, Am J Physiol Renal Physiol 278:F830–8 (2000).

    CAS  PubMed  Google Scholar 

  88. Y. Shima, K. Nakao, T. Nakashima, et al., Activation of caspase-8 in transforming growth factor-beta-induced apoptosis of human hepatoma cells, Hepatol 30:1215–1222 (1999).

    Article  CAS  Google Scholar 

  89. I. Fabregat, B. Herrera, M. Fernández, et al., Epidermal growth factor impairs the cytochrome C-caspase-3 apoptotic pathway induced by transforming growth factor beta in rat fetal hepatocyctes via a phosphoinositide 3-kinase-dependent pathway., Hepatol 32:528–535 (2000).

    Article  CAS  Google Scholar 

  90. P. Golstein, and A. Wyllie, T cell death and transforming growth factor betal, J Exp Med 194:F19–F21 (2001).

    Article  CAS  PubMed  Google Scholar 

  91. N. Shaheen, W. Straus, and R. Sandler, Chemoprevention of gastrointestinal malignancies with nonsteroidal antiinflammatory drugs, Cancer 94:950–963 (2002).

    Article  CAS  PubMed  Google Scholar 

  92. R. S. Sandler, S. Halabi, J. A. Baron, et al., A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer, N Engl J Med 348:883–90 (2003).

    CAS  PubMed  Google Scholar 

  93. J._A. Baron, B. F. Cole, R. S. Sandier, et al., A randomized trial of aspirin to prevent colorectal adenomas, N Engl J Med 348:891–9 (2003).

    Article  CAS  PubMed  Google Scholar 

  94. E. Giovannucci, K. Egan, D. Hunter, et al., Aspirin and the risk of colorectal cancer in women, New Engl J Med 333:609–614 (1995).

    Article  CAS  PubMed  Google Scholar 

  95. A. Paganini-Hill, Aspirin and the prevention of colorectal cancer: a review of the evidence, Semin Surg Oncol 10:158–164 (1994).

    CAS  PubMed  Google Scholar 

  96. A. Denda, Q. Tang, T. Endoh, et al., Prevention by acetylsalicylic acid of liver cirrhosis and carcinogenesis as well as generations of 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances caused by a choline-deficient, L-amino aciddefined diet in rats., Carcinogenesis 15:1279–1283 (1994).

    CAS  PubMed  Google Scholar 

  97. N. Mahmoud, S. Boolbol, A. Dannenberg, et al., The sulfide metabolite of sulindac prevents tumors and restores enterocyte apoptosis in a murine model of familial adenomatous polyposis, Carcinogenesis 19:87–91 (1998A).

    Article  CAS  PubMed  Google Scholar 

  98. H. Thompson, C. Jiang, J. Lu, et al., Sulfone metabolite of sulindac inhibits mammary carcinogenesis, Cancer Res 57:267–271 (1997).

    CAS  PubMed  Google Scholar 

  99. P. Pasricha, A. Bedi, K. O’Connor, et al., The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis, Gastroenterology 109:994–998 (1995).

    CAS  PubMed  Google Scholar 

  100. M. Cruz-Correa, L. Hylind, K. Romans, S. Booker, and F. Giardiello, Long-term treatment with sulindac in familial adenomatous polyposis: a prospective cohort study., Gastroenterology 122:641–645 (2002).

    CAS  PubMed  Google Scholar 

  101. F. Giardiello, V. Yang, L. Hylind, et al., Primary chemoprevention of familial adenomatous polyposis with sulindac, N Engl J Med 346:1054–1059 (2002).

    Article  CAS  PubMed  Google Scholar 

  102. J. Rüschoff, S. Wallinger, W. Dietmaier, et al., Aspirin suppresses the mutator phenotype associated with hereditary nonpolyposis colorectal cancer by genetic seletion, Proc Natl Acad Sci USA 95:11301–11306 (1998).

    PubMed  Google Scholar 

  103. R. Hanif, A. Pittas, Y. Feng, et al., Effects of nonsteroidal anti-inflammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandin-independent pathway, Biochem Pharmacol 52:237–245 (1996).

    Article  CAS  PubMed  Google Scholar 

  104. Z. Dong, C. Huang, R. Brown, and W. Ma, Inhibition of activator protein 1 activity and neoplastic transformation by aspirin., J Biol Chem 272:9962–9970 (1997).

    CAS  PubMed  Google Scholar 

  105. G. Levy, Prostaglandin H synthases, nonsteroidal anti-inflammatory drugs, and colon cancer, FASEB J 11:234–247 (1997).

    CAS  PubMed  Google Scholar 

  106. G. Piazza, A. Rahm, T. Finn, et al., Apoptosis primarily accounts for the growthinhibitory properties of sulindac metabolites and involves a mechanism that is independent of cyclooxygenase inhibition, cell cycle arrest, and p53 induction. Cancer Res 57:2452–2459 (1997).

    CAS  PubMed  Google Scholar 

  107. D. Elder, and C. Paraskeva, NSAIDS to prevent colorectal cancer: A question of sensitivity., Gastroenterol 113:1999–2008 (1997).

    CAS  Google Scholar 

  108. B. Bellosillo, M. Piqué, M. Barragán, et al., Aspirin and salicylate induce apoptosis and activation of caspases in B-cell chronic lymphocytic leukemia cells., Blood 92:1406–1414 (1998).

    CAS  PubMed  Google Scholar 

  109. E.-H. Han, N. Arber, H. Yamamoto, et al., Effects of sulindac and its metabolites on growth and apoptosis in human mammary epithelial and breast carcinoma cell lines. Breast Cancer Res Treatment 48:195–203 (1998).

    CAS  Google Scholar 

  110. S. Shiff, and B. Rigas, The role of cyclooxygenase inhibition in the antineoplastic effects of nonsteroidal antiinflammatory drugs (NSAIDs), J Exper Med 190:445–450 (1999).

    Article  CAS  Google Scholar 

  111. N. Mahmoud, A. Dannenberg, J. Mestre, et al., Aspirin prevents tumors in a murine model of familial adenomatous polyposis, Surgery 124:225–231 (1998B).

    CAS  PubMed  Google Scholar 

  112. R. Gupta, and R. Dubois, Aspirin, NSAIDs, and colon cancer prevention mechanisms?, Gastroenterol 114:1095–1098 (1998).

    CAS  Google Scholar 

  113. M. Whitehouse, Uncoupling of oxidative phosphorylation in a connective tissue (cartilage) and liver mitochondria by salicylate analogues: Relationship of structure to activity, Biochem Pharmacol 13:319–336 (1964).

    Article  CAS  PubMed  Google Scholar 

  114. M. Mehlman, R. Tobin, and E. Sporn, Oxidative phosphorylation and respiration by rat liver mitochondria from aspirin-treated rats, Biochem Pharmacol 21:3279–3285 (1972).

    CAS  PubMed  Google Scholar 

  115. T. Mahmud, S. Rafi, D. Scott, J. Wrigglesworth, and I. Bjarnason, Nonsteroidal antiinflammatory drugs and uncoupling of mitochondrial oxidative phosphorylation. Arthritis Rheum 39:1998–2003 (1996).

    CAS  PubMed  Google Scholar 

  116. M. Jacob, I. Bjarnason, and R. J. Simpson, Effects of indomethacin on energy metabolism in rat jejunal tissue in vivo, Clin Sci (Lond) 102:541–6 (2002).

    CAS  Google Scholar 

  117. R. Haas, W. Parker, Jr, D. Stumpf, and L. Eguren, Salicylate-induced loose couplinga; protonmotive force measurements, Biochem Pharmacol 34:900–902 (1985).

    Article  CAS  PubMed  Google Scholar 

  118. Y. Chen, J. Cai, T. J. Murphy, and D. P. Jones, Overexpressed human mitochondrial thioredoxin confers resistance to oxidant-induced apoptosis in human osteosarcoma cells, J Biol Chem 277:33242–8 (2002).

    CAS  PubMed  Google Scholar 

  119. A. E. Damdimopoulos, A. Miranda-Vizuete, M. Pelto-Huikko, J. A. Gustafsson, and G. Spyrou, Human mitochondrial thioredoxin. Involvement in mitochondrial membrane potential and cell death, J Biol Chem 277:33249–57 (2002).

    Article  CAS  PubMed  Google Scholar 

  120. T. Tanaka, F. Hosoi, Y. Yamaguchi-Iwai, et al., Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis, Embo J 21:1695–703 (2002).

    Article  CAS  PubMed  Google Scholar 

  121. C. Sen, and L. Packer, Antioxidant and redox regulation of gene transcription, FASEB J 10:709–720 (1996).

    CAS  PubMed  Google Scholar 

  122. V. Lakshminarayanan, E. Drab-Weiss, and K. Roebuck, H2O2and tumor necrosis factor-alpha induce differential binding of the redox-responsive transcription factors AP-1 and NF-kappaB to the interleukin-8 promoter in endothelial and epithelial cells, J Biol Chem 273:32670–32678 (1998).

    Article  CAS  PubMed  Google Scholar 

  123. E. Shaulian, and M. Karin, AP-1 as a regulator of cell life and death, Nat Cell Biol 4:E131–6 (2002).

    Article  CAS  PubMed  Google Scholar 

  124. T. Vos, H. Van Goor, L. Tuyt, et al., Expression of inducible nitric oxide synthase in endotoxemic rat hepatocytes is dependent on the cellular glutathione status, Hepatology 29:421–426 (1999).

    CAS  PubMed  Google Scholar 

  125. K. Yamamoto, T. Arakawa, N. Ueda, and S. Yamamoto, Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells, J Biol Chem 270:31315–31320 (1995).

    CAS  PubMed  Google Scholar 

  126. M. Tamatani, Y. Che, H. Matsuzaki, et al., Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFkappaB activation in primary hippocampal neurons, J Biol Chem 274:8531–8538 (1999).

    Article  CAS  PubMed  Google Scholar 

  127. W. Zong, L. Edelstein, C. Chen, J. Bash, and C. Gélinas, The prosurvival Bcl-2 homolog Bfl-2/A1 is a direct transcriptional target of NF-kappaB that blocks TNFalpha-induced apoptosis, Genes Development 13:382–387 (1999).

    CAS  PubMed  Google Scholar 

  128. F. Lee, Y. Li, H. Zhu, et al., Tumor necrosis factor increases mitochondrial oxidant production and induces expression of uncoupling protein-2 in the regenerating mouse liver, Hepatology 29:677–687 (1999).

    Article  CAS  PubMed  Google Scholar 

  129. K. Echtay, D. Roussel, J. St-Pierre, et al., Superoxide activates mitochondrial uncoupling proteins., Nature 415:96–99 (2002).

    Article  CAS  PubMed  Google Scholar 

  130. A. Beg, and D. Baltimore, An essential role for NF-kappaB in preventing TNFalpha-induced cell death., Science 274:782–784 (1996).

    Article  CAS  PubMed  Google Scholar 

  131. C.-Y. Wang, M. Mayo, and J. Baldwin, AS TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB, Science 274:784–787 (1996).

    Article  CAS  PubMed  Google Scholar 

  132. D. Van Antwerp, S. Martin, T. Kafri, D. Green, and I. Verma, Suppression of TNFalpha-induced apoptosis by NF-kappaB, Science 274:787–789 (1996).

    PubMed  Google Scholar 

  133. M. Karin, and A. Lin, NF-kappaB at the crossroads of life and death, Nat Immunol 3:221–227 (2002).

    Article  CAS  PubMed  Google Scholar 

  134. O. Micheau, and J. Tschopp, Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes, Cell 114:181–90 (2003).

    Article  CAS  PubMed  Google Scholar 

  135. N. Perkins, The Rel/NF-kappa B family: friend and foe, Trends Biochem Sci 25:434–440 (2000).

    Article  CAS  PubMed  Google Scholar 

  136. D. Rolfe, A. Hulbert, and M. Brand, Characteristics of mitochondrial proton leak and control of oxidative phosphorylation in the major oxygen-consuming tissues of the rat, Biochim Biophys Acta 1188:405–416 (1994).

    PubMed  Google Scholar 

  137. E. Kopp, and S. Ghosh, Inhibition of NF-kappa B by sodium salicylate and aspirin, Science 265:956–959 (1994).

    CAS  PubMed  Google Scholar 

  138. M. Grilli, M. Pizzi, M. Memo, and P. Spano, Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation, Science 274:1383–1385 (1996).

    Article  CAS  PubMed  Google Scholar 

  139. T. McDade, R. Perugini, F. Vittimberga, Jr, R. Carrigan, and M. Callery, Salicylates inhibit NF-kappaB activation and enhance TNF-alpha-induced apoptosis in human pancreatic cancer cells, J Surg Res 83:56–61 (1999).

    Article  CAS  PubMed  Google Scholar 

  140. L. Klampfer, J. Cammenga, H. Wisniewski, and S. Nimer, Sodium salicylate activates caspases and induces apoptosis of myeloid leukemia cell lines, Blood 93:2386–2394 (1999).

    CAS  PubMed  Google Scholar 

  141. K. W. Oh, T. Qian, D. A. Brenner, and J. J. Lemasters, Salicylate enhances necrosis and apoptosis mediated by the mitochondrial permeability transition, Toxicol Sci 73:44–52 (2003).

    Article  CAS  PubMed  Google Scholar 

  142. M. Yin, Y. Yamamoto, and R. Gaynor, The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta, Nature 396:77–80 (1998).

    CAS  PubMed  Google Scholar 

  143. J. Kim, Y. Kim, J. Fillmore, et al., Prevention of fat-induced insulin resistance by salicylate, J Clin Invest 108:437–446 (2001).

    CAS  PubMed  Google Scholar 

  144. M. Yuan, N. Konstantopoulos, J. Lee, et al, Reversal of obesity-and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta, Science 293:1673–1677 (2001).

    Article  CAS  PubMed  Google Scholar 

  145. G. Jiang, Q. Dallas-Yang, F. Liu, D. E. Moller, and B. B. Zhang, Salicylic acid reverses phorbol 12-myristate-13-acetate (PMA)-and tumor necrosis factor alpha (TNFalpha)-induced insulin receptor substrate 1 (IRS1) serine 307 phosphorylation and insulin resistance in human embryonic kidney 293 (HEK293) cells, J Biol Chem 278:180–6 (2003).

    CAS  PubMed  Google Scholar 

  146. Y. Tokumitsu, S. Lee, and M. Ui, In vitro effects of nonsteroidal anti-inflammatory drugs on oxidative phosphorylation in rats liver mitochondria, Biochem Pharmacol 26:2101–2106 (1977).

    CAS  PubMed  Google Scholar 

  147. K. Kawai, H. Shiojiri, H. Fukushima, and Y. Nozawa, The inhibition of mitochondrial respiration by indomethacin, a non-steroid anti-inflammatory agent possessing inhibitory effect on prostaglandin biosynthesis, Res Commun Chem Pathol Pharmacol 48:267–274 (1985).

    CAS  PubMed  Google Scholar 

  148. P. McDougall, A. Markham, I. Cameron, and A. Sweetman, The mechanism of inhibition of mitochondrial oxidative phosphorylation by the nonsteroidal antiinflammatory agent diflunisal, Biochem Pharmacol 32:2595–2598 (1983).

    Article  CAS  PubMed  Google Scholar 

  149. Y. Yamamoto, M. Yin, K. Lin, and R. Gaynor, Sulindac inhibits activation of the NF-kappaB pathway, J Biol Chem 274:27307–27314 (1999).

    CAS  PubMed  Google Scholar 

  150. M. Taylor, K. Lawson, N. Ignatenko, et al., Sulindac sulfone inhibits K-rasdependent cyclooxygenase-2 expression in human colon cancer cells, Cancer Res 60:6607–6610 (2000).

    CAS  PubMed  Google Scholar 

  151. M. Wick, G. Hurteau, C. Dessev, et al., Peroxisome proliferator-activated receptorgamma is a target of nonsteroidal anti-inflammatory drugs mediating cyclooxygenaseindependent inhibition of lung cancer cell growth, Mol Pharmacol 62:1207–14 (2002).

    Article  CAS  PubMed  Google Scholar 

  152. E. Freneaux, B. Fromenty, A. Berson, et al., Stereoselective and nonstereoselective effects of ibuprofen enantiomers on mitochondrial beta-oxidation of fatty acids., J Pharmacol Exp Ther 255:529–535 (1990).

    CAS  PubMed  Google Scholar 

  153. R. Kundu, G. Getz, and J. Tonsgard, Induction of (omega-1)-oxidation of monocarboxylic acids by acetylsalicylic acid, J Lipid Res 34:1187–1199 (1993).

    CAS  PubMed  Google Scholar 

  154. Y. Cai, A. Sohlenius, K. Andersson, C. Sundberg, and J. Depierre, Effects of acetylsalicylic acid on parameters related to peroxisome proliferation in mouse liver., Biochem Pharmacol 47:2213–2219 (1994).

    Article  CAS  PubMed  Google Scholar 

  155. E. Rekka, E. Ayalogu, D. Lewis, G. Gibson, and C. Ioannides, Induction of hepatic microsomal CYP4A activity and of peroxisomal beta-oxidation by two non-steroidal anti-inflammatory drugs, Arch Toxicol 68:73–78 (1994).

    Article  CAS  PubMed  Google Scholar 

  156. P. Craven, K. Thornburg, and F. Derubertis, Sustained increase in the proliferation of rat colonic mucosa during chronic treatment with aspirin., Gastroenterology 94:567–575 (1988).

    CAS  PubMed  Google Scholar 

  157. J. Lehmann, J. Lenhard, B. Oliver, G. Ringold, and S. Kliewer, Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs, J Biol Chem 272:3406–3410 (1997).

    CAS  PubMed  Google Scholar 

  158. M. Jaradat, B. Wongsud, S. Phornchirasilp, et al., Activation of peroxisome proliferator-activated receptor isoforms and inhibition of prostaglandin H(2) synthases by ibuprofen, naproxen, and indomethacin, Biochem Pharmacol 62:1587–1595 (2001).

    Article  CAS  PubMed  Google Scholar 

  159. B. Forman, J. Chen, and R. Evans, Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta., Proc Natl Acad Sci USA 94:4312–4317 (1997).

    CAS  PubMed  Google Scholar 

  160. K. Yu, W. Bayona, C. Kallen, et al., Differential activation of peroxisome proliferator-activated receptors by eiconsanoids, J Biol Chem 270:2397–23983 (1995).

    Google Scholar 

  161. H. Sheng, J. Shao, M. Washington, and R. DuBois, Prostaglandin E2 increases growth and motility of colorectal carcinoma cells, J Biol Chem 276:18075–18081 (2001).

    CAS  PubMed  Google Scholar 

  162. C. Prager, H. Schö, M. Nikfardjam, et al., Clofibrate elevates enzyme activities of the tricarboxylic acid cycle in rat liver, J Lipid Res 34:359–364 (1993).

    CAS  PubMed  Google Scholar 

  163. B. Wolfe, J. Kane, R. Havel, and H. Brewster, Mechanism of the hypolipemic effect of clofibrate in postabsorptive man, J Clin Invest 52:2146–2159 (1973).

    CAS  PubMed  Google Scholar 

  164. M. Laker, and P. Mayes, The immediate and long term effects of clofibrate on the metabolism of the perfused rat liver, Biochem Pharmacol 28:2813–2827 (1979).

    Article  CAS  PubMed  Google Scholar 

  165. K. Yamamoto, N. Fukuda, L. Zhang, and T. Sakai, Altered hepatic metabolism of fatty acids in rats fed a hypolipidaemic drug, fenofibrate, Pharmacol Res 33:337–342 (1996).

    Article  CAS  PubMed  Google Scholar 

  166. M. Poynter, and R. Daynes, Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappaB signaling, and reduces inflammatory cytokine production in aging, J Biol Chem 273:32833–32841 (1998).

    Article  CAS  PubMed  Google Scholar 

  167. X. Xu, L. Sansores-Garcia, X. Chen, N. Matijevic-Aleksic, M. Du, and K. Wu, Suppression of inducible cyclooxygenase 2 gene transcription by aspirin and sodium salicylate, Proc Natl Acad Sci USA 96:5292–5297 (1999).

    CAS  PubMed  Google Scholar 

  168. B. A. Narayanan, N. K. Narayanan, B. Simi, and B. S. Reddy, Modulation of inducible nitric oxide synthase and related proinflammatory genes by the omega-3 fatty acid docosahexaenoic acid in human colon cancer cells, Cancer Res 63:972–9 (2003).

    CAS  PubMed  Google Scholar 

  169. R. Gupta, J. Tan, W. Krause, et al., Prostacyclin-mediated activation of peroxisome proliferator-activated receptor in colorectal cancer, Proc Natl Acad Sci USA 97:13275–13280 (2000).

    Article  CAS  PubMed  Google Scholar 

  170. M. Smith, G. Hawcroft, and M. Hull, The effect of non-steroidal anti-inflammatory drugs on human colorectal cancer cells: evidence of different mechanisms of action, Eur J Cancer 36:664–674 (2000).

    Article  CAS  PubMed  Google Scholar 

  171. S. Arico, S. Pattingre, C. Bauvy, et al., Celecoxib induces apoptosis by inhibiting 3-phosphoinositide-dependent protein kinase-1 activity in the human colon cancer HT-29 cell line, J Biol Chem 277:27613–21 (2002).

    Article  CAS  PubMed  Google Scholar 

  172. G. Sigthorsson, R. J. Simpson, M. Walley, et al., COX-1 and 2, intestinal integrity, and pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in mice, Gastroenterology 122:1913–23 (2002).

    Article  CAS  PubMed  Google Scholar 

  173. T. Crew, D. Elder, and C. Paraskeva, A cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drug enhances the growth inhibitory effect of butyrate in colorectal carcinoma cells expressing COX-2 protein: regulation of COX-2 by butyrate., Carcinogenesis 21:69–77 (2000).

    Article  CAS  PubMed  Google Scholar 

  174. B. Rigas, and S. Shiff, Is inhibition of cyclooxygenase required for the chemopreventive effect of NSAIDs in colon cancer? A model reconciling the current contradiction, Med Hypotheses 54:210–215 (2000).

    Article  CAS  PubMed  Google Scholar 

  175. T. He, T. Chan, B. Vogelstein, and K. Kinzler, PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs, Cell 99:335–345 (1999).

    Article  CAS  PubMed  Google Scholar 

  176. J. Peters, S. Lee, W. Li, et al., Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta), Molec Cell Biol 20:5119–5128 (2000B).

    CAS  PubMed  Google Scholar 

  177. B. Poligone, and A. Baldwin, Positive and negative regulation of NF-kappa B by COX-2: Roles of different prostaglandins, J Biol Chem 276:38658–38664 (2001).

    Article  CAS  PubMed  Google Scholar 

  178. J. Scheiman, and G. Elta, Gastroduodenal mucosal damage with salsalate versus aspirin: results of experimental models and endoscopic studies in humans, Semin Arthritis Rheumatism 20:121–127 (1990).

    CAS  Google Scholar 

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(2004). Metabolic Effects of Antiproliferative Agents. In: Integration of Metabolism, Energetics, and Signal Transduction. Springer, Boston, MA. https://doi.org/10.1007/0-306-48529-X_6

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