Skip to main content

MODULATION OF TRANSCRIPTION FACTORS BY CURCUMIN

  • Chapter

Part of the book series: ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY ((AEMB,volume 595))

Abstract

Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer’s disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1. B. B. Aggarwal and S. Shishodia, Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol 71, 1397–1421 (2006).

    Article  PubMed  CAS  Google Scholar 

  2. 2. S. Shishodia, G. Sethi, and B. B. Aggarwal, Curcumin: getting back to the roots. Ann NY Acad Sci 1056, 206–217 (2005).

    Article  PubMed  CAS  Google Scholar 

  3. 3. B. B. Aggarwal, Nuclear factor-kappaB: the enemy within. Cancer Cell 6, 203–208 (2004).

    Article  PubMed  CAS  Google Scholar 

  4. 4. S. Shishodia and B. B. Aggarwal, Nuclear factor-kappaB: A friend or a foe in cancer? Biochem Pharmacol 68, 1071–1080 (2004).

    Article  PubMed  CAS  Google Scholar 

  5. 5. A. S. Baldwin, Jr., Series introduction: the transcription factor NF-kappaB and human disease. J Clin Invest 107, 3–6 (2001).

    PubMed  CAS  Google Scholar 

  6. 6. H. L. Pahl, Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18, 6853–6866 (1999).

    Article  PubMed  CAS  Google Scholar 

  7. 7. D. K. Giri and B. B. Aggarwal, Constitutive activation of NF-kappaB causes resistance to apoptosis in human cutaneous T cell lymphoma HuT-78 cells. Autocrine role of tumor necrosis factor and reactive oxygen intermediates. J Biol Chem 273, 14,008–14,014 (1998).

    Article  CAS  Google Scholar 

  8. 8. H. Lee, M. Wu, F. A. La Rosa, M. P. Duyao, A J. Buckler, and G. E. Sonenshein, Role of the Rel-family of transcription factors in the regulation of c-myc gene transcription and apoptosis of WEHI 231 murine B-cells. Curr Top Microbiol Immunol 194, 247–255 (1995).

    PubMed  CAS  Google Scholar 

  9. 9. C. Y. Wang, M. W. Mayo, and A. S. Baldwin, Jr. TNF- and cancer therapy-induced apoptosis: Potentiation by inhibition of NF-kappaB. Science 274, 784–787 (1996).

    Article  PubMed  CAS  Google Scholar 

  10. 10. A. C. Bharti, N. Donato, S. Singh, and B. B. Aggarwal, Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 101, 1053–1062 (2003).

    Article  PubMed  CAS  Google Scholar 

  11. 11. R. J. Anto, Mukhopadhyay, K. Denning, and B. B. Aggarwal, Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: Its suppression by ectopic expression of Bcl-2 and Bcl-xl. Carcinogenesis 23, 143–150 (2002).

    Article  PubMed  CAS  Google Scholar 

  12. 12. N. Mori, M. Fujii, S. Ikeda, Y. Yamada, M. Tomonaga, D. W. Ballard, and N. Yamamoto, Constitutive activation of NF-kappaB in primary adult T-cell leukemia cells. Blood 93, 2360–2368 (1999).

    PubMed  CAS  Google Scholar 

  13. 13. C. E. Bueso-Ramos, F. C. Rocha, S. Shishodia, L. J. Medeiros, H. M. Kantarjian, S. Vadhan-Raj, Z. Estrov, T. L. Smith, M. H. Nguyen, and B. B. Aggarwal, Expression of constitutively active nuclear factor-kappa B RelA transcription factor in blasts of acute myeloid leukemia. Hum Pathol 35, 246–253 (2004).

    Article  PubMed  CAS  Google Scholar 

  14. 14. T. Dorai, Y. C. Cao, B. Dorai, R. Buttyan, and A. E. Katz, Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate 47, 293–303 (2001).

    Article  PubMed  CAS  Google Scholar 

  15. 15. H. Nakshatri, P. Bhat-Nakshatri, D. A. Martin, DR. J. Goulet, Jr., and G. W. Sledge, Jr., Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol Cell Biol 17, 3629–3639 (1997).

    PubMed  CAS  Google Scholar 

  16. 16. Z. Wang, Y. Zhang, S. Banerjee, Y. Li, and F. H. Sarkar, Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer 106, 2503–2513 (2006).

    Article  PubMed  CAS  Google Scholar 

  17. 17. S. Singh and B. B. Aggarwal, Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J Biol Chem 270, 24,995–25,000 (1995).

    Article  CAS  Google Scholar 

  18. 18. S. Aggarwal, H. Ichikawa, Y. Takada, S. K. Sandur, S. Shishodia, and B. B. Aggarwal, Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation. Mol Pharmacol 69, 195–206 (2006).

    PubMed  CAS  Google Scholar 

  19. 19. C. Jobin, C. A. Bradham, M. P. Russo, B. Juma, A. S. Narula, D. A. Brenner, and R. B. Sartor, Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. J Immunol 163, 3474–3483 (1999).

    PubMed  CAS  Google Scholar 

  20. 20. S. M. Plummer, K. A. Holloway, M. M. Manson, R. J. Munks, A. Kaptein, S. Farrow, and L. Howells, Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene 18, 6013–6020 (1999).

    Article  PubMed  CAS  Google Scholar 

  21. 21. R. K. Thomas, M. L. Sos, T. Zander, O. Mani, A. Popov, D. Berenbrinker, S. Smola-Hess, J. L. Schultze, and J. Wolf, Inhibition of nuclear translocation of nuclear factor-kappaB despite lack of functional IkappaBalpha protein overcomes multiple defects in apoptosis signaling in human B-cell malignancies. Clin Cancer Res 11, 8186–8194 (2005).

    Article  PubMed  CAS  Google Scholar 

  22. 22. S. Shishodia, P. Potdar, C. G. Gairola, and B. B. Aggarwal, Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF-kappaB activation through inhibition of IkappaBalpha kinase in human lung epithelial cells: Correlation with suppression of COX-2, MMP-9 and cyclin D1. Carcinogenesis 24, 1269–1279 (2003).

    Article  PubMed  CAS  Google Scholar 

  23. 23. S. Shishodia, H. M. Amin, R. Lai, and B. B. Aggarwal, Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Biochem Pharmacol 70, 700–713 (2005).

    Article  PubMed  CAS  Google Scholar 

  24. 24. S. Philip and G. C. Kundu, Osteopontin induces nuclear factor kappa B-mediated promatrix metalloproteinase-2 activation through I kappa B alpha /IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways. J Biol Chem 278, 14,487–14,497 (2003).

    CAS  Google Scholar 

  25. 25. M. Zheng, S. Ekmekcioglu, E. T. Walch, C. H. Tang, and E. R. Grimm, Inhibition of nuclear factor-kappaB and nitric oxide by curcumin induces G2/M cell cycle arrest and apoptosis in human melanoma cells. Melanoma Res 14, 165–171 (2004).

    Article  PubMed  CAS  Google Scholar 

  26. 26. K. H. Kim, H. Y. Park, J. H. Nam, J. E. Park, J. Y Kim, M. I. Park, K. O. Chung, K. Y. Park, and J. Y. Koo, The inhibitory effect of curcumin on the growth of human colon cancer cells (HT-29, WiDr) in vitro. Korean J Gastroenterol 45, 277–284 (2005).

    PubMed  Google Scholar 

  27. 27. B. B. Aggarwal, S. Shishodia, Y. Takada, S. Banerjee, R. A. Newman, C. E. Bueso-Ramos, and J. E. Price, Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res 11, 7490–7498 (2005).

    Article  PubMed  CAS  Google Scholar 

  28. 28. R. Eferl and E. F. Wagner, AP-1: A double-edged sword in tumorigenesis. Nat Rev Cancer 3, 859–868 (2003).

    Article  PubMed  CAS  Google Scholar 

  29. 29. M. Takakura, S. Kyo, M. Inoue, W. E. Wright, and J. W. Shay, Function of AP-1 in transcription of the telomerase reverse transcriptase gene (TERT) in human and mouse cells. Mol Cell Biol 25, 8037–8043 (2005).

    Article  PubMed  CAS  Google Scholar 

  30. 30. T. Bowman, M. A. Broome, D. Sinibaldi, W. Wharton, W. J. Pledger, J. M. Sedivy, R. Irby, T. Yeatman, S. A. Courtneidge, and R. Jove, Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci USA 98, 7319–7324 (2001).

    Article  PubMed  CAS  Google Scholar 

  31. 31. J. F. Bromberg, C. M. Horvath, D. Besser, W.W. Lathem, and J. E. Darnell, Jr., Stat3 activation is required for cellular transformation by v-src. Mol Cell Biol 18, 2553–2558 (1998).

    PubMed  CAS  Google Scholar 

  32. 32. F. C. Hsieh, G. Cheng, and J. Lin, Evaluation of potential Stat3-regulated genes in human breast cancer. Biochem Biophys Res Commun 335, 292–299 (2005).

    Article  PubMed  CAS  Google Scholar 

  33. 33. J. Coyle-Rink, L. Del Valle, T. Sweet, K. Khalili, and S. Amini, Developmental expression of Wnt signaling factors in mouse brain. Cancer Biol Ther 1, 640–645 (2002).

    PubMed  CAS  Google Scholar 

  34. 34. Y. Kim, R. C. Sills, and C. D. Houle, Overview of the molecular biology of hepatocellular neoplasms and hepatoblastomas of the mouse liver. Toxicol Pathol 33, 175–180 (2005).

    Article  PubMed  CAS  Google Scholar 

  35. 35. Y. Zhai, R. Wu, D. R. Schwartz, D. Darrah, H. Reed, F. T. Kolligs, M. T. Nieman, E. R. Fearon, and K. K. Cho, Role of beta-catenin/T-cell factor-regulated genes in ovarian endometrioid adenocarcinomas. Am J Pathol 160, 1229–1238 (2002).

    PubMed  CAS  Google Scholar 

  36. 36. M. M. Montano, A. K. Jaiswal, and B. S. Katzenellenbogen, Transcriptional regulation of the human quinone reductase gene by antiestrogen-liganded estrogen receptor-alpha and estrogen receptor-beta. J Biol Chem 273, 25,443–25,449 (1998).

    Article  CAS  Google Scholar 

  37. 37. M. Zhu and W. E. Fahl, Functional characterization of transcription regulators that interact with the electrophile response element. Biochem Biophys Res Commun 289, 212–219 (2001).

    Article  PubMed  CAS  Google Scholar 

  38. 38. A. Chen, J. Xu, and A. C. Johnson, Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene 25, 278–287 (2006).

    PubMed  Google Scholar 

  39. 39. M. Fu, X. Zhu, J. Zhang, J. Liang, Y. Lin, L. Zhao, M. U. Ehrengruber, and Y. E. Chen, Egr-1 target genes in human endothelial cells identified by microarray analysis. Gene 315, 33–41 (2003).

    Article  PubMed  CAS  Google Scholar 

  40. 40. Y. Moon, F. G. Bottone, Jr., M. F. McEntee, and T. E. Eling, Suppression of tumor cell invasion by cyclooxygenase inhibitors is mediated by thrombospondin-1 via the early growth response gene Egr-1. Mol Cancer Ther 4, 1551–1558 (2005).

    Article  PubMed  CAS  Google Scholar 

  41. 41. L. Stefano, J. Al Sarraj, O. G. Rossler, C. Vinson, and G. Thiel, Up-regulation of tyrosine hydroxylase gene transcription by tetradecanoylphorbol acetate is mediated by the transcription factors Ets-like protein-1 (Elk-1) and Egr-1. J Neurochem 97, 92–104 (2006).

    Article  PubMed  CAS  Google Scholar 

  42. 42. D. Xiao, D. Chinnappan, R. Pestell, C. Albanese, and H. C. Weber, Bombesin regulates cyclin D1 expression through the early growth response protein Egr-1 in prostate cancer cells. Cancer Res 65, 9934–9942 (2005).

    Article  PubMed  CAS  Google Scholar 

  43. 43. J. Svaren, T. Ehrig, S. A. Abdulkadir, M. U. Ehrengruber, M. A. Watson, and J. Milbrandt, EGR1 target genes in prostate carcinoma cells identified by microarray analysis. J Biol Chem 275, 38,524–38,531 (2000).

    Article  CAS  Google Scholar 

  44. 44. J. Li, M. Tan, L. Li, D. Pamarthy, T. S. Lawrence, and Y. Sun, SAK, a new polo-like kinase, is transcriptionally repressed by p53 and induces apoptosis upon RNAi silencing. Neoplasia 7, 312–323 (2005).

    Article  PubMed  CAS  Google Scholar 

  45. 45. Y. Sun, p53 and its downstream proteins as molecular targets of cancer. Mol Carcinog 45, 409–415 (2006).

    Article  PubMed  CAS  Google Scholar 

  46. 46. A. C. Wild, H. R. Moinova, and R. T. Mulcahy, Regulation of gamma-glutamylcysteine synthetase subunit gene expression by the transcription factor Nrf2. J Biol Chem 274, 33,627–33,636 (1999).

    Article  CAS  Google Scholar 

  47. 47. J. Kim and G. A. Coetzee, Prostate specific antigen gene regulation by androgen receptor. J Cell Biochem 93, 233–241 (2004).

    Article  PubMed  CAS  Google Scholar 

  48. 48. P. Petrusz, D. A. Jeyaraj, and G. Grossman, Microarray analysis of androgen-regulated gene expression in testis: the use of the androgen-binding protein (ABP)-transgenic mouse as a model. Reprod Biol Endocrinol 3, 70 (2005).

    Article  PubMed  CAS  Google Scholar 

  49. 49. I. Bogacka, H. Xie, G. A. Bray, and S. R. Smith, The effect of pioglitazone on peroxisome proliferator-activated receptor-gamma target genes related to lipid storage in vivo. Diabetes Care 27, 1660–1667 (2004).

    Article  PubMed  CAS  Google Scholar 

  50. 50. P. Delerive, F. Martin-Nizard, G. Chinetti, F. Trottein, J. C. Fruchart, J. Najib, P. Duriez, and B. Staels, Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circ Res 85, 394–402 (1999).

    PubMed  CAS  Google Scholar 

  51. 51. S. Hummasti and P. Tontonoz, The peroxisome proliferator-activated receptor N-terminal domain controls isotype-selective gene expression and adipogenesis. Mol Endocrinol 20, 1261–1275 (2006).

    Article  PubMed  CAS  Google Scholar 

  52. 52. P. Dikshit, A. Goswami, A. Mishra, M. Chatterjee, and N. R. Jana, Curcumin induces stress response, neurite outgrowth and prevent NF-kappaB activation by inhibiting the proteasome function. Neurotox Res 9, 29–37 (2006).

    Article  PubMed  CAS  Google Scholar 

  53. 53. C. H. Yeh, Y. M. Lin, Y. C. Wu, and P. J. Lin, Inhibition of NF-kappa B activation can attenuate ischemia/reperfusion-induced contractility impairment via decreasing cardiomyocytic proinflammatory gene up-regulation and matrix metalloproteinase expression. J Cardiovasc Pharmacol 45, 301–309 (2005).

    Article  PubMed  CAS  Google Scholar 

  54. 54. S. Wessler, P. Muenzner, T. F. Meyer, and M. Naumann, The anti-inflammatory compound curcumin inhibits Neisseria gonorrhoeae-induced NF-kappaB signaling, release of pro-inflammatory cytokines/chemokines and attenuates adhesion in late infection. Biol Chem 386, 481–490 (2005).

    Article  PubMed  CAS  Google Scholar 

  55. 55. M. Karin, Z. Liu, and E. Zandi, AP-1 function and regulation. Curr Opin Cell Biol 9, 240–246 (1997).

    Article  PubMed  CAS  Google Scholar 

  56. 56. Y. Xia, C. Makris, B. Su, E. Li, J. Yang, G. R. Nemerow, and M. Karin, MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration. Proc Natl Acad Sci USA 97, 5243–5248 (2000).

    Article  PubMed  CAS  Google Scholar 

  57. 57. C. Huang, J. Li, W. Y. Ma, and Z. Dong, JNK activation is required for JB6 cell transformation induced by tumor necrosis factor-alpha but not by 12-O-tetradecanoylphorbol-13-acetate. J Biol Chem 274, 29,672–29,676 (1999).

    CAS  Google Scholar 

  58. 58. M. T. Huang, T. Lysz, T. Ferraro, T. F. Abidi, J. D. Laskin, and A. H. Conney, Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Res 51, 813–819 (1991).

    PubMed  CAS  Google Scholar 

  59. 59. Y. R. Chen and T. H. Tan, Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin. Oncogene 17, 173–178 (1998).

    Article  PubMed  CAS  Google Scholar 

  60. 60. A. Bierhaus, Y. Zhang, P. Quehenberger, T. Luther, M. Haase, M. Muller, N. Mackman, R. Ziegler, and P. P. Nawroth, The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-kappa B. Thromb Haemost 77, 772–782 (1997).

    PubMed  CAS  Google Scholar 

  61. 61. D. A. Dickinson, K. E. Iles, H. Zhang, V. Blank, and H. J. Forman, Curcumin alters EpRE and AP-1 binding complexes and elevates glutamate-cysteine ligase gene expression. FASEB J 17, 473–475 (2003).

    PubMed  CAS  Google Scholar 

  62. 62. M. Tomita, H. Kawakami, J. N. Uchihara, T. Okudaira, M. Masuda, N. Takasu, T. Matsuda, T. Ohta, Y. Tanaka, and N. Mori, Curcumin suppresses constitutive activation of AP-1 by downregulation of JunD protein in HTLV-1-infected T-cell lines. Leuk Res 30, 313–321 (2006).

    Article  PubMed  CAS  Google Scholar 

  63. 63. C. S. Divya and M. R. Pillai, Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis. Mol Carcinog 45, 320–332 (2006).

    Article  PubMed  CAS  Google Scholar 

  64. 64. C. Polytarchou, M. Hatziapostolou, and E. Papadimitriou, Hydrogen peroxide stimulates proliferation and migration of human prostate cancer cells through activation of activator protein-1 and up-regulation of the heparin affin regulatory peptide gene. J Biol Chem 280, 40,428–40,435 (2005).

    Article  CAS  Google Scholar 

  65. 65. B. K. Prusty and B. C. Das, Constitutive activation of transcription factor AP-1 in cervical cancer and suppression of human papillomavirus (HPV) transcription and AP-1 activity in HeLa cells by curcumin. Int J Cancer 113, 951–960 (2005).

    Article  PubMed  CAS  Google Scholar 

  66. 66. M. S. Squires, E. A. Hudson, L. Howells, S. Sale, C. E. Houghton, J. L. Jones, L. H. Fox, M. Dickens, S. A. Prigent, and M. M. Manson, Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells. Biochem Pharmacol 65, 361–376 (2003).

    Article  PubMed  CAS  Google Scholar 

  67. 67. M. L. Cho, Y. O. Jung, Y. M. Moon, S. Y. Min, C. H. Yoon, S. H. Lee, S. H. Park, C. S. Cho, D. M. Jue, and H. Y. Kim, Interleukin-18 induces the production of vascular endothelial growth factor (VEGF) in rheumatoid arthritis synovial fibroblasts via AP-1-dependent pathways. Immunol Lett 103, 159–166 (2006).

    Article  PubMed  CAS  Google Scholar 

  68. 68. U. R. Pendurthi and L. V. Rao, Suppression of transcription factor Egr-1 by curcumin. Thromb Res 97, 179–189 (2000).

    Article  PubMed  CAS  Google Scholar 

  69. 69. J. E. Darnell, Jr., I. M. Kerr, and G. R. Stark, Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264, 1415–1421 (1994).

    Article  PubMed  CAS  Google Scholar 

  70. 70. J. E. Darnell, Jr., STATs and gene regulation. Science 277, 1630–1635 (1997).

    Article  PubMed  CAS  Google Scholar 

  71. 71. C. L. Yu, D. J. Meyer, G. S. Campbell, A. C. Larner, C. Carter-Su, J. Schwartz, and R. Jove, Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science 269, 81–83 (1995).

    Article  PubMed  CAS  Google Scholar 

  72. 72. J. R. Grandis, S. D. Drenning, A. Chakraborty, M. Y. Zhou, Q. Zeng, A.S. Pitt, and D. J. Tweardy, Requirement of Stat3 but not Stat1 activation for epidermal growth factor receptor- mediated cell growth In vitro. J Clin Invest 102, 1385–1392 (1998).

    Article  PubMed  CAS  Google Scholar 

  73. 73. N. Carlesso, D. A. Frank, and J. D. Griffin, Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. J Exp Med 183, 811–820 (1996).

    Article  PubMed  CAS  Google Scholar 

  74. 74. R. M. Weber-Nordt, C. Egen, J. Wehinger, W. Ludwig, V. Gouilleux-Gruart, R. Mertelsmann, and J. Finke, Constitutive activation of STAT proteins in primary lymphoid and myeloid leukemia cells and in Epstein-Barr virus (EBV)-related lymphoma cell lines. Blood 88, 809–816 (1996).

    PubMed  CAS  Google Scholar 

  75. 75. A. C. Bharti, N. Donato, and B. B. Aggarwal, Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol 171, 3863–3871 (2003).

    PubMed  CAS  Google Scholar 

  76. 76. H. Y. Kim, E. J. Park, E. H. Joe, and I. Jou, Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia. J Immunol 171, 6072–6079 (2003).

    PubMed  CAS  Google Scholar 

  77. 77. W. Q. Li, F. Dehnade, and M. Zafarullah, Oncostatin M-induced matrix metalloproteinase and tissue inhibitor of metalloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. J Immunol 166, 3491–3498 (2001).

    PubMed  CAS  Google Scholar 

  78. 78. C. Natarajan and J. J. Bright, Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12 signaling through Janus kinase-STAT pathway in T lymphocytes. J Immunol 168, 6506–6513 (2002).

    PubMed  CAS  Google Scholar 

  79. 79. W. H. Chen, Y. Chen, G. H. Cui, J. X. Gu, D. Hu, W. K. Chen, and X. G. Li, Effect of curcumin on STAT5 signaling pathway in primary CML cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi 12, 572–576 (2004).

    PubMed  CAS  Google Scholar 

  80. 80. W. H. Chen, Y. Chen, J. X. Gu, and J. He, Effect of curcumin on STAT5 signaling molecule in K562 cells. Zhonghua Xue Ye Xue Za Zhi 25, 151–153 (2004).

    PubMed  Google Scholar 

  81. 81. J. Xu, Y. Fu, and A. Chen, Activation of peroxisome proliferator-activated receptor-gamma contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth. Am J Physiol Gastrointest Liver Physiol 285, G20–G30 (2003).

    PubMed  CAS  Google Scholar 

  82. 82. A. Chen and J. Xu, Activation of PPARγ by curcumin inhibits Moser cell growth and mediates suppression of gene expression of cyclin D1 and EGFR. Am J Physiol Gastrointest Liver Physiol 288, G447–G456 (2005).

    Article  PubMed  CAS  Google Scholar 

  83. 83. S. Zheng and A. Chen, Curcumin suppresses the expression of extracellular matrix genes in activated hepatic stellate cells by inhibiting gene expression of connective tissue growth factor. Am J Physiol Gastrointest Liver Physiol 290, G883–G893 (2006).

    Article  PubMed  CAS  Google Scholar 

  84. 84. A. M. Siddiqui, X. Cui, R. Wu, W. Dong, M. Zhou, M. Hu, H. H. Simms and P. Wang, The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by up-regulation of peroxisome proliferator-activated receptor-gamma. Crit Care Med 34, 1874–1882 (2006).

    Article  PubMed  CAS  Google Scholar 

  85. 85. W. S. el-Deiry, T. Tokino, V. E. Velculescu, D. B. Levy, R. Parsons, J. M. Trent, D. Lin, W. E. Mercer, K. W. Kinzler, and B. Vogelstein, WAF1, a potential mediator of p53 tumor suppression. Cell 75, 817–825 (1993).

    Article  PubMed  CAS  Google Scholar 

  86. 86. B. Vogelstein and K. W. Kinzler, p53 function and dysfunction. Cell 70, 523–526 (1992).

    Article  PubMed  CAS  Google Scholar 

  87. 87. S. S. Han, S. T. Chung, D. A. Robertson, D. Ranjan, and S. Bondada, Curcumin causes the growth arrest and apoptosis of B cell lymphoma by downregulation of egr-1, c-myc, bcl-XL, NF-kappa B, and p53. Clin Immunol 93, 152–161 (1999).

    Article  PubMed  CAS  Google Scholar 

  88. 88. J. A. Bush, K. J. Cheung, Jr., and G Li, Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53. Exp Cell Res 271, 305–314 (2001).

    Article  PubMed  CAS  Google Scholar 

  89. 89. T. Choudhuri, S. Pal, M. L. Agwarwal, T. Das, and G. Sa, Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction. FEBS Lett 512, 334–340 (2002).

    Article  PubMed  CAS  Google Scholar 

  90. 90. T. Choudhuri, S. Pal, T. Das, and G. Sa, Curcumin selectively induces apoptosis in deregulated cyclin D1-expressed cells at G2 phase of cell cycle in a p53-dependent manner. J Biol Chem 280, 20,059–20,068 (2005).

    Article  CAS  Google Scholar 

  91. 91. M. J. Park, E. H. Kim, I. C. Park, H. C. Lee, S. H. Woo, J. Y. Lee, Y. J. Hong, C. H. Rhee, S. H. Choi, B. S. Shim, et al., Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells by up-regulating cyclin-dependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53. Int J Oncol 21, 379–383 (2002).

    PubMed  CAS  Google Scholar 

  92. 92. A. Liontas and H. Yeger, Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma. Anticancer Res 24, 987–998 (2004).

    PubMed  CAS  Google Scholar 

  93. 93. A. S. Jaiswal, B. P. Marlow, N. Gupta, and S. Narayan, Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene 21, 8414–8427 (2002).

    Article  PubMed  CAS  Google Scholar 

  94. 94. N. N. Mahmoud, A. M. Carothers, D. Grunberger, R. T. Bilinski, M. R. Churchill, C. Martucci, H. L. Newmark, and M. M. Bertagnolli, Plant phenolics decrease intestinal tumors in an animal model of familial adenomatous polyposis. Carcinogenesis 21, 921–927 (2000).

    Article  PubMed  CAS  Google Scholar 

  95. 95. E. Balogun, M. Hoque, P. Gong, E. Killeen, C. J. Green, R. Foresti, J. Alam, and R. Motterlini, Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J 371, 887–895 (2003).

    Article  PubMed  CAS  Google Scholar 

  96. 96. S. A. Rushworth, R. M. Ogborne, C. A. Charalambos, and M. A. O'Connell, Role of protein kinase C delta in curcumin-induced antioxidant response element-mediated gene expression in human monocytes. Biochem Biophys Res Commun 341, 1007–1016 (2006).

    Article  PubMed  CAS  Google Scholar 

  97. 97. A. Banning, S. Deubel, D. Kluth, Z. Zhou, and R. Brigelius-Flohe, The GI-GPx gene is a target for Nrf2. Mol Cell Biol 25, 4914–4923 (2005).

    Article  PubMed  CAS  Google Scholar 

  98. 98. K. Nakamura, Y. Yasunaga, T. Segawa, D. Ko, J. W. Moul, S. Srivastava, and J. S. Rhim, Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. Int J Oncol 21, 825–830 (2002).

    PubMed  CAS  Google Scholar 

  99. 99. M. G. Marcu, Y. J. Jung, S. Lee, E. J. Chung, M. J. Lee, J. Trepel, and L. Neckers, Curcumin is an inhibitor of p300 histone acetylatransferase. Med Chem 2, 169–174 (2006).

    Article  PubMed  CAS  Google Scholar 

  100. 100. K. Balasubramanyam, R. A. Varier, M. Altaf, V. Swaminathan, N. B. Siddappa, U. Ranga, and T. K. Kundu, Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem 279, 51,163–51,171 (2004).

    CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer

About this chapter

Cite this chapter

Shishodia, S., Singh, T., Chaturvedi, M.M. (2007). MODULATION OF TRANSCRIPTION FACTORS BY CURCUMIN. In: Aggarwal, B.B., Surh, YJ., Shishodia, S. (eds) The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY, vol 595. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-46401-5_4

Download citation

Publish with us

Policies and ethics