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Scientifica
Volume 2012, Article ID 757890, 13 pages
http://dx.doi.org/10.6064/2012/757890
Review Article

A Neutraceutical by Design: The Clinical Application of Curcumin in Colonic Inflammation and Cancer

Division of Gastroenterology, Department of Medicine, The University of British Columbia, Vancouver, BC, V5Z 1M9, Canada

Received 10 July 2012; Accepted 26 August 2012

Academic Editors: A. Asai and W. Vogel

Copyright © 2012 D. Soni and B. Salh. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. S. Sandler, J. E. Everhart, M. Donowitz et al., “The burden of selected digestive diseases in the United States,” Gastroenterology, vol. 122, no. 5, pp. 1500–1511, 2002. View at Google Scholar · View at Scopus
  2. F. Kamangar, G. M. Dores, and W. F. Anderson, “Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world,” Journal of Clinical Oncology, vol. 24, no. 14, pp. 2137–2150, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. D. M. Parkin, F. Bray, J. Ferlay, and P. Pisani, “Global cancer statistics, 2002,” CA Cancer Journal for Clinicians, vol. 55, no. 2, pp. 74–108, 2005. View at Google Scholar · View at Scopus
  4. J. Xie and S. H. Itzkowitz, “Cancer in inflammatory bowel disease,” World Journal of Gastroenterology, vol. 14, no. 3, pp. 378–389, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. D. C. Baumgart and W. J. Sandborn, “Inflammatory bowel disease: clinical aspects and established and evolving therapies,” The Lancet, vol. 369, no. 9573, pp. 1641–1657, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. S. H. Itzkowitz and X. Yio, “Inflammation and cancer—IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation,” American Journal of Physiology, vol. 287, no. 1, pp. G7–G17, 2004. View at Publisher · View at Google Scholar · View at Scopus
  7. S. R. Targan, S. B. Hanauer, S. J. H. van Deventer et al., “A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor α for Crohn's disease,” The New England Journal of Medicine, vol. 337, no. 15, pp. 1029–1035, 1997. View at Publisher · View at Google Scholar · View at Scopus
  8. K. Sugimoto, H. Hanai, K. Tozawa et al., “Curcumin prevents and ameliorates trinitrobenzene sulfonic acid-induced colitis in mice,” Gastroenterology, vol. 123, no. 6, pp. 1912–1922, 2002. View at Publisher · View at Google Scholar · View at Scopus
  9. S. Perkins, R. D. Verschoyle, K. Hill et al., “Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a model of familial adenomatous polyposis,” Cancer Epidemiology, Biomarkers & Prevention, vol. 11, pp. 535–540, 2002. View at Google Scholar
  10. S. Perkins, A. R. Clarke, W. Steward, and A. Gescher, “Age-related difference in susceptibility of Apc(Min/+) mice towards the chemopreventive efficacy of dietary aspirin and curcumin,” British Journal of Cancer, vol. 88, pp. 1480–1483, 2003. View at Google Scholar
  11. A. Ukil, S. Maity, S. Karmakar, N. Datta, J. R. Vedasiromoni, and P. K. Das, “Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis,” British Journal of Pharmacology, vol. 139, no. 2, pp. 209–218, 2003. View at Publisher · View at Google Scholar · View at Scopus
  12. B. Salh, K. Assi, V. Templeman et al., “Curcumin attenuates DNB-induced murine colitis,” American Journal of Physiology, vol. 285, no. 1, pp. G235–G243, 2003. View at Google Scholar · View at Scopus
  13. Y. T. Jian, G. F. Mai, J. D. Wang, Y. L. Zhang, R. C. Luo, and Y. X. Fang, “Preventive and therapeutic effects of NF-kappaB inhibitor curcumin in rats colitis induced by trinitrobenzene sulfonic acid,” World Journal of Gastroenterology, vol. 11, no. 12, pp. 1747–1752, 2005. View at Google Scholar · View at Scopus
  14. H. Jiang, C.-S. Deng, M. Zhang, and J. Xia, “Curcumin-attenuated trinitrobenzene sulphonic acid induces chronic colitis by inhibiting expression of cyclooxygenase-2,” World Journal of Gastroenterology, vol. 12, no. 24, pp. 3848–3853, 2006. View at Google Scholar · View at Scopus
  15. M. Zhang, C. S. Deng, J. J. Zheng, and J. Xia, “Curcumin regulated shift from Th1 to Th2 in trinitrobenzene sulphonic acid-induced chronic colitis,” Acta Pharmacologica Sinica, vol. 27, no. 8, pp. 1071–1077, 2006. View at Publisher · View at Google Scholar · View at Scopus
  16. M. V. Venkataranganna, M. Rafiq, S. Gopumadhavan, G. Peer, U. V. Babu, and S. K. Mitra, “NCB-02 (standardized Curcumin preparation) protects dinitrocholorobenzene-induced colitis through down-regulation of NFκ-B and iNOS,” World Journal of Gastroenterology, vol. 13, no. 7, pp. 1103–1107, 2007. View at Google Scholar · View at Scopus
  17. L. Camacho-Barquero, I. Villegas, J. M. Sánchez-Calvo et al., “Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis,” International Immunopharmacology, vol. 7, no. 3, pp. 333–342, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. L. Martelli, E. Ragazzi, F. Di Mario et al., “A potential role for the vanilloid receptor TRPV1 in the therapeutic effect of curcumin in dinitrobenzene sulphonic acid-induced colitis in mice,” Neurogastroenterology and Motility, vol. 19, no. 8, pp. 668–674, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. Y. Deguchi, A. Andoh, O. Inatomi et al., “Curcumin prevents the development of dextran sulfate sodium (DSS)-induced experimental colitis,” Digestive Diseases and Sciences, vol. 52, no. 11, pp. 2993–2998, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. C. Billerey-Larmonier, J. K. Uno, N. Larmonier et al., “Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent,” Inflammatory Bowel Diseases, vol. 14, no. 6, pp. 780–793, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. C. B. Larmonier, J. K. Uno, K. M. Lee et al., “Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice suggest an IL-10-dependent mechanism of protection,” American Journal of Physiology, vol. 295, no. 5, pp. G1079–G1091, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. K. Nones, Y. E. M. Dommels, S. Martell et al., “The effects of dietary curcumin and rutin on colonic inflammation and gene expression in multidrug resistance gene-deficient (mdr1a-/-) mice, a model of inflammatory bowel diseases,” The British Journal of Nutrition, vol. 101, no. 2, pp. 169–181, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. A. Lubbad, M. A. Oriowo, and I. Khan, “Curcumin attenuates inflammation through inhibition of TLR-4 receptor in experimental colitis,” Molecular and Cellular Biochemistry, vol. 322, no. 1-2, pp. 127–135, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. Q. Jia, I. Ivanov, Z. Z. Zlatev et al., “Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice,” The British Journal of Nutrition, vol. 106, no. 4, pp. 519–529, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. G. Shoba, D. Joy, T. Joseph, M. Majeed, R. Rajendran, and P. S. S. R. Srinivas, “Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers,” Planta Medica, vol. 64, no. 4, pp. 353–356, 1998. View at Publisher · View at Google Scholar · View at Scopus
  26. A. L. Chen, C. H. Hsu, J. K. Lin et al., “Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions,” Anticancer Research, vol. 21, no. 4, pp. 2895–2900, 2001. View at Google Scholar · View at Scopus
  27. C. D. Lao, M. T. Ruffin, D. Normolle et al., “Dose escalation of a curcuminoid formulation,” BMC Complementary and Alternative Medicine, vol. 6, article 10, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. R. A. Sharma, H. R. McLelland, K. A. Hill et al., “Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer,” Clinical Cancer Research, vol. 7, no. 7, pp. 1894–1900, 2001. View at Google Scholar · View at Scopus
  29. R. A. Sharma, S. A. Euden, S. L. Platton et al., “Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance,” Clinical Cancer Research, vol. 10, no. 20, pp. 6847–6854, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. G. Garcea, D. J. L. Jones, R. Singh et al., “Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration,” British Journal of Cancer, vol. 90, no. 5, pp. 1011–1015, 2004. View at Publisher · View at Google Scholar · View at Scopus
  31. G. Garcea, D. P. Berry, D. J. L. Jones et al., “Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences,” Cancer Epidemiology Biomarkers and Prevention, vol. 14, no. 1, pp. 120–125, 2005. View at Google Scholar · View at Scopus
  32. P. R. Holt, S. Katz, and R. Kirshoff, “Curcumin therapy in inflammatory bowel disease: a pilot study,” Digestive Diseases and Sciences, vol. 50, no. 11, pp. 2191–2193, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. H. Hanai, T. Iida, K. Takeuchi et al., “Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial,” Clinical Gastroenterology and Hepatology, vol. 4, no. 12, pp. 1502–1506, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. P. M. Barnes, B. Bloom, and R. L. Nahin, “Complementary and alternative medicine use among adults and children: United States, 2007,” National Health Statistics Reports, no. 12, pp. 1–23, 2008. View at Google Scholar · View at Scopus
  35. R. J. Hilsden, M. J. Verhoef, H. Rasmussen, A. Porcino, and J. C. C. Debruyn, “Use of complementary and alternative medicine by patients with inflammatory bowel disease,” Inflammatory Bowel Diseases, vol. 17, no. 2, pp. 655–662, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. K. L. Goh and S. D. Xiao, “Inflammatory bowel disease: a survey of the epidemiology in Asia,” Journal of Digestive Diseases, vol. 10, no. 1, pp. 1–6, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. S. M. Montgomery, D. L. Morris, R. E. Pounder, and A. J. Wakefield, “Asian ethnic origin and the risk of inflammatory bowel disease,” European Journal of Gastroenterology and Hepatology, vol. 11, no. 5, pp. 543–546, 1999. View at Google Scholar · View at Scopus
  38. B. K. Mangat, C. Evaschen, T. Lee, E. M. Yoshida, and B. Salh, “Ethnic variation in the annual rates of adult inflammatory bowel disease in hospitalized patients in Vancouver, British Columbia,” Canadian Journal of Gastroenterology, vol. 25, no. 2, pp. 73–77, 2011. View at Google Scholar · View at Scopus
  39. R. Virk, S. Gill, E. Yoshida, S. Radley, and B. Salh, “Racial differences in the incidence of colorectal cancer,” Canadian Journal of Gastroenterology, vol. 24, no. 1, pp. 47–51, 2010. View at Google Scholar · View at Scopus
  40. H. P. T. Ammon and M. A. Wahl, “Pharmacology of Curcuma longa,” Planta Medica, vol. 57, no. 1, pp. 1–7, 1991. View at Google Scholar · View at Scopus
  41. P. Anand, S. G. Thomas, A. B. Kunnumakkara et al., “Biological activities of curcumin and its analogues (Congeners) made by man and mother nature,” Biochemical Pharmacology, vol. 76, no. 11, pp. 1590–1611, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. S. K. Sandur, A. Deorukhkar, M. K. Pandey et al., “Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible nf-kappab activity,” International Journal of Radiation Oncology Biology Physics, vol. 75, no. 2, pp. 534–542, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. S. Somasundaram, N. A. Edmund, D. T. Moore, G. W. Small, Y. Y. Shi, and R. Z. Orlowski, “Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer,” Cancer Research, vol. 62, no. 13, pp. 3868–3875, 2002. View at Google Scholar · View at Scopus
  44. N. Chainani-Wu, “Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa),” Journal of Alternative and Complementary Medicine, vol. 9, no. 1, pp. 161–168, 2003. View at Google Scholar · View at Scopus
  45. M. Nagabhushan and S. V. Bhide, “Nonmutagenicity of curcumin and its antimutagenic action versus chili and capsaicin,” Nutrition and Cancer, vol. 8, no. 3, pp. 201–210, 1986. View at Google Scholar · View at Scopus
  46. P. Anand, A. B. Kunnumakkara, R. A. Newman, and B. B. Aggarwal, “Bioavailability of curcumin: problems and promises,” Molecular Pharmaceutics, vol. 4, no. 6, pp. 807–818, 2007. View at Publisher · View at Google Scholar · View at Scopus
  47. S. L. Thomas, D. Zhong, W. Zhou et al., “EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and inhibits HIF-1,” Cell Cycle, vol. 7, no. 15, pp. 2409–2417, 2008. View at Google Scholar · View at Scopus
  48. B. T. Kurien, A. Singh, H. Matsumoto, and R. H. Scofield, “Improving the solubility and pharmacological efficacy of curcumin by heat treatment,” Assay and Drug Development Technologies, vol. 5, no. 4, pp. 567–576, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. S. K. Sandur, M. K. Pandey, B. Sung et al., “Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism,” Carcinogenesis, vol. 28, no. 8, pp. 1765–1773, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. S. C. Gupta, S. Prasad, J. H. Kim et al., “Multitargeting by curcumin as revealed by molecular interaction studies,” Natural Product Reports, vol. 28, pp. 1937–1955, 2011. View at Google Scholar
  51. S. Ali, A. Ahmad, S. Banerjee et al., “Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF,” Cancer Research, vol. 70, no. 9, pp. 3606–3617, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. B. B. Aggarwal, S. Shishodia, S. K. Sandur, M. K. Pandey, and G. Sethi, “Inflammation and cancer: how hot is the link?” Biochemical Pharmacology, vol. 72, no. 11, pp. 1605–1621, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. S. Singh and B. B. Aggarwal, “Activation of transcription factor nf-kappa b is suppressed by curcumin (diferuloylmethane),” The Journal of Biological Chemistry, vol. 270, pp. 24995–25000, 1995. View at Publisher · View at Google Scholar · View at Scopus
  54. C. Jobin, C. A. Bradham, M. P. Russo et al., “Curcumin blocks cytokine-mediated NF-κB activation and proinflammatory gene expression by inhibiting inhibitory factor I-κB kinase activity,” Journal of Immunology, vol. 163, no. 6, pp. 3474–3483, 1999. View at Google Scholar · View at Scopus
  55. 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 IκBα kinase and Akt activation,” Molecular Pharmacology, vol. 69, no. 1, pp. 195–206, 2006. View at Publisher · View at Google Scholar · View at Scopus
  56. J. H. Cho, “The genetics and immunopathogenesis of inflammatory bowel disease,” Nature Reviews Immunology, vol. 8, no. 6, pp. 458–466, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Huang, L. Zhao, K. Kim, S. L. Dong, and D. H. Hwang, “Inhibition of Nod2 signaling and target gene expression by curcumin,” Molecular Pharmacology, vol. 74, no. 1, pp. 274–281, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. S. Kreuz, D. Siegmund, P. Scheurich, and H. Wajant, “NF-κB inducers upregulate cFLIP, a cycloheximide-sensitive inhibitor of death receptor signaling,” Molecular and Cellular Biology, vol. 21, no. 12, pp. 3964–3973, 2001. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Tamatani, Y. H. Che, H. Matsuzaki et al., “Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFκB activation in primary hippocampal neurons,” The Journal of Biological Chemistry, vol. 274, no. 13, pp. 8531–8538, 1999. View at Publisher · View at Google Scholar · View at Scopus
  60. W. X. Zong, L. C. Edelstein, C. Chen, J. Bash, and C. Gélinas, “The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-κB that blocks TNFα-induced apoptosis,” Genes and Development, vol. 13, no. 4, pp. 382–387, 1999. View at Google Scholar · View at Scopus
  61. C. Stehlik, R. de Martin, I. Kumabashiri, J. A. Schmid, B. R. Binder, and J. Lipp, “Nuclear factor (NF)-κB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor α-induced apoptosis,” Journal of Experimental Medicine, vol. 188, no. 1, pp. 211–216, 1998. View at Publisher · View at Google Scholar · View at Scopus
  62. C. Y. Wang, M. W. Mayo, R. G. Korneluk, D. V. Goeddel, and A. S. Baldwin, “NF-κB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c- IAP2 to suppress caspase-8 activation,” Science, vol. 281, no. 5383, pp. 1680–1683, 1998. View at Publisher · View at Google Scholar · View at Scopus
  63. L. Zhu, S. Fukuda, G. Cordis, D. K. Das, and N. Maulik, “Anti-apoptotic protein survivin plays a significant role in tubular morphogenesis of human coronary arteriolar endothelial cells by hypoxic preconditioning,” FEBS Letters, vol. 508, no. 3, pp. 369–374, 2001. View at Publisher · View at Google Scholar · View at Scopus
  64. A. B. Kunnumakkara, P. Diagaradjane, P. Anand et al., “Curcumin sensitizes human colorectal cancer to capecitabine by modulation of cyclin D1, COX-2, MMP-9, VEGF and CXCR4 expression in an orthotopic mouse model,” International Journal of Cancer, vol. 125, no. 9, pp. 2187–2197, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Moussavi, K. Assi, A. Gómez-Muñoz, and B. Salh, “Curcumin mediates ceramide generation via the de novo pathway in colon cancer cells,” Carcinogenesis, vol. 27, no. 8, pp. 1636–1644, 2006. View at Publisher · View at Google Scholar · View at Scopus
  66. Y. Cheng, A. Kozubek, L. Ohlsson, B. Sternby, and R. D. Duan, “Curcumin decreases acid sphingomyelinase activity in colon cancer caco-2 cells,” Planta Medica, vol. 73, no. 8, pp. 725–730, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. J. F. Schmedtje Jr., Y. S. Ji, W. L. Liu, R. N. DuBois, and M. S. Runge, “Hypoxia induces cyclooxygenase-2 via the NF-κB p65 transcription factor in human vascular endothelial cells,” The Journal of Biological Chemistry, vol. 272, no. 1, pp. 601–608, 1997. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Hinz, D. Krappmann, A. Eichten, A. Heder, C. Scheidereit, and M. Strauss, “NF-κB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition,” Molecular and Cellular Biology, vol. 19, no. 4, pp. 2690–2698, 1999. View at Google Scholar · View at Scopus
  69. M. P. Duyao, A. J. Buckler, and G. E. Sonenshein, “Interaction of an NF-κB-like factor with a site upstream of the c-myc promoter,” Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 12, pp. 4727–4731, 1990. View at Publisher · View at Google Scholar · View at Scopus
  70. D. G. Binion, M. F. Otterson, and P. Rafiee, “Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition,” Gut, vol. 57, no. 11, pp. 1509–1517, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. T. Yokoo and M. Kitamura, “Dual regulation of IL-1β-mediated matrix metalloproteinase-9 expression in mesangial cells by NF-KB and AP-1,” American Journal of Physiology, vol. 270, no. 1, pp. F123–F130, 1996. View at Google Scholar · View at Scopus
  72. G. Helbig, K. W. Christopherson, P. Bhat-Nakshatri et al., “NF-κB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4,” The Journal of Biological Chemistry, vol. 278, no. 24, pp. 21631–21638, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. D. Šošić, J. A. Richardson, K. Yu, D. M. Ornitz, and E. N. Olson, “Twist regulates cytokine gene expression through a negative feedback loop that represses NF-κB activity,” Cell, vol. 112, no. 2, pp. 169–180, 2003. View at Publisher · View at Google Scholar · View at Scopus
  74. S. M. Plummer, K. A. Holloway, M. M. Manson et al., “Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex,” Oncogene, vol. 18, no. 44, pp. 6013–6020, 1999. View at Publisher · View at Google Scholar · View at Scopus
  75. L. Adam, A. Mazumdar, T. Sharma, T. R. Jones, and R. Kumar, “A three-dimensional and temporo-spatial model to study invasiveness of cancer cells by heregulin and prostaglandin E21,” Cancer Research, vol. 61, no. 1, pp. 81–87, 2001. View at Google Scholar · View at Scopus
  76. H. Sheng, J. Shao, M. K. Washington, and R. N. DuBois, “Prostaglandin e2 increases growth and motility of colorectal carcinoma cells,” The Journal of Biological Chemistry, vol. 276, no. 21, pp. 18075–18081, 2001. View at Publisher · View at Google Scholar · View at Scopus
  77. W. S. Chen, S. J. Wei, J. M. Liu, M. Hsiao, J. Kou-Lin, and W. K. Yang, “Tumor invasiveness and liver metastasis of colon cancer cells correlated with cyclooxygenase-2 (cox-2) expression and inhibited by a cox-2-selective inhibitor, etodolac,” International Journal of Cancer, vol. 91, pp. 894–899, 2001. View at Google Scholar
  78. M. J. Thun, M. M. Namboodiri, and C. W. Heath Jr., “Aspirin use and reduced risk of fatal colon cancer,” The New England Journal of Medicine, vol. 325, no. 23, pp. 1593–1596, 1991. View at Google Scholar · View at Scopus
  79. M. J. Thun, S. J. Henley, and C. Patrono, “Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues,” Journal of the National Cancer Institute, vol. 94, no. 4, pp. 252–266, 2002. View at Google Scholar · View at Scopus
  80. J. L. Arbiser, N. Klauber, R. Rohan et al., “Curcumin is an in vivo inhibitor of angiogenesis,” Molecular Medicine, vol. 4, no. 6, pp. 376–383, 1998. View at Google Scholar · View at Scopus
  81. D. G. Binion, J. Heidemann, M. S. Li, V. M. Nelson, M. F. Otterson, and P. Rafiee, “Vascular cell adhesion molecule-1 expression in human intestinal microvascular endothelial cells is regulated by PI 3-kinase/Akt/MAPK/NF- κB: inhibitory role of curcumin,” American Journal of Physiology, vol. 297, no. 2, pp. G259–G268, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. D. Thaloor, A. K. Singh, G. S. Sidhu, P. V. Prasad, H. K. Kleinman, and R. K. Maheshwari, “Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin,” Cell Growth and Differentiation, vol. 9, no. 4, pp. 305–312, 1998. View at Google Scholar · View at Scopus
  83. M. K. Bae, S. H. Kim, J. W. Jeong et al., “Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1,” Oncology Reports, vol. 15, no. 6, pp. 1557–1562, 2006. View at Google Scholar · View at Scopus
  84. J. S. Shim, J. H. Kim, H. Y. Cho et al., “Irreversible inhibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin,” Chemistry and Biology, vol. 10, no. 8, pp. 695–704, 2003. View at Publisher · View at Google Scholar · View at Scopus
  85. S. Yodkeeree, W. Chaiwangyen, S. Garbisa, and P. Limtrakul, “Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA,” Journal of Nutritional Biochemistry, vol. 20, no. 2, pp. 87–95, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. J. Epstein, G. Docena, T. T. MacDonald, and I. R. Sanderson, “Curcumin suppresses p38 mitogen-activated protein kinase activation, reduces IL-1β and matrix metalloproteinase-3 and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease,” British Journal of Nutrition, vol. 103, no. 6, pp. 824–832, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. P. J. Moos, K. Edes, J. E. Mullally, and F. A. Fitzpatrick, “Curcumin impairs tumor suppressor p53 function in colon cancer cells,” Carcinogenesis, vol. 25, no. 9, pp. 1611–1617, 2004. View at Publisher · View at Google Scholar · View at Scopus
  88. 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-X(l), NF-κB, and p53,” Clinical Immunology, vol. 93, no. 2, pp. 152–161, 1999. View at Publisher · View at Google Scholar · View at Scopus
  89. G. Song, Y. B. Mao, Q. F. Cai, L. M. Yao, G. L. Ouyang, and S. D. Bao, “Curcumin induces human HT-29 colon adenocarcinoma cell apoptosis by activating p53 and regulating apoptosis-related protein expression,” Brazilian Journal of Medical and Biological Research, vol. 38, no. 12, pp. 1791–1798, 2005. View at Google Scholar · View at Scopus
  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,” The Journal of Biological Chemistry, vol. 280, no. 20, pp. 20059–20068, 2005. View at Publisher · View at Google Scholar · View at Scopus
  91. G. P. Collett and F. C. Campbell, “Curcumin induces c-jun N-terminal kinase-dependent apoptosis in HCT116 human colon cancer cells,” Carcinogenesis, vol. 25, no. 11, pp. 2183–2189, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. M. Hu, Q. Du, I. Vancurova et al., “Proapoptotic effect of curcumin on human neutrophils: activation of the p38 mitogen-activated protein kinase pathway,” Critical Care Medicine, vol. 33, no. 11, pp. 2571–2578, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. 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,” American Journal of Physiology, vol. 288, no. 3, pp. G447–G456, 2005. View at Publisher · View at Google Scholar · View at Scopus
  94. C. V. Rao, B. Simi, and B. S. Reddy, “Inhibition by dietary curcumin of azoxymethane-induced ornithine decarboxylase, tyrosine protein kinase, arachidonic acid metabolism and aberrant crypt foci formation in the rat colon,” Carcinogenesis, vol. 14, no. 11, pp. 2219–2225, 1993. View at Google Scholar · View at Scopus
  95. J. M. Kim, S. Araki, D. J. Kim et al., “Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation,” Carcinogenesis, vol. 19, no. 1, pp. 81–85, 1998. View at Publisher · View at Google Scholar · View at Scopus
  96. B. Joe and B. R. Lokesh, “Dietary n-3 fatty acids, curcumin and capsaicin lower the release of lysosomal enzymes and eicosanoids in rat peritoneal macrophages,” Molecular and Cellular Biochemistry, vol. 203, no. 1-2, pp. 153–161, 2000. View at Google Scholar · View at Scopus
  97. D. J. B. Marks and A. W. Segal, “Innate immunity in inflammatory bowel disease: a disease hypothesis,” Journal of Pathology, vol. 214, no. 2, pp. 260–266, 2008. View at Publisher · View at Google Scholar · View at Scopus
  98. C. B. Larmonier, M. T. Midura-Kiela, R. Ramalingam et al., “Modulation of neutrophil motility by curcumin: implications for inflammatory bowel disease,” Inflammatory Bowel Diseases, vol. 17, no. 2, pp. 503–515, 2011. View at Publisher · View at Google Scholar · View at Scopus
  99. I. Villegas, S. Sánchez-Fidalgo, and C. A. de la Lastra, “Chemopreventive effect of dietary curcumin on inflammation-induced colorectal carcinogenesis in mice,” Molecular Nutrition and Food Research, vol. 55, no. 2, pp. 259–267, 2011. View at Publisher · View at Google Scholar · View at Scopus
  100. E. A. Murphy, J. M. Davis, J. L. McClellan, B. T. Gordon, and M. D. Carmichael, “Curcumin's effect on intestinal inflammation and tumorigenesis in the ApcMin/+ mouse,” Journal of Interferon and Cytokine Research, vol. 31, no. 2, pp. 219–226, 2011. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Kubota, M. Shimizu, H. Sakai et al., “Preventive effects of curcumin on the development of azoxymethane-induced colonic preneoplastic lesions in male c57bl/ksj-db/db obese mice,” Nutrition and Cancer, vol. 64, no. 1, pp. 72–79, 2012. View at Google Scholar
  102. K. Assi and B. Salh, “Curcumin reduces neoplasms in a model of colitis-associated cancer through effects on ILK, b-catenin, cyclin D, NF-kB and Akt,” Gastroenterology A412, 2011.
  103. B. Chandran and A. Goel, “A randomized, pilot study to assess the efficacy and safety of curcumin in patients with active rheumatoid arthritis,” Phytotherapy Research. In press.
  104. D. Banji, J. Pinnapureddy, O. J. F. Banji, A. Saidulu, and M. S. Hayath, “Synergistic activity of curcumin with methotrexate in ameliorating Freund's Complete Adjuvant induced arthritis with reduced hepatotoxicity in experimental animals,” European Journal of Pharmacology, vol. 668, pp. 293–298, 2011. View at Publisher · View at Google Scholar · View at Scopus
  105. M. C. Y. Heng, M. K. Song, J. Harker, and M. K. Heng, “Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters,” British Journal of Dermatology, vol. 143, no. 5, pp. 937–949, 2000. View at Publisher · View at Google Scholar · View at Scopus
  106. R. R. Satoskar, S. J. Shah, and S. G. Shenoy, “Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation,” International Journal of Clinical Pharmacology Therapy and Toxicology, vol. 24, no. 12, pp. 651–654, 1986. View at Google Scholar · View at Scopus
  107. B. Lal, A. K. Kapoor, O. P. Asthana et al., “Efficacy of curcumin in the management of chronic anterior uveitis,” Phytotherapy Research, vol. 13, pp. 318–322, 1999. View at Google Scholar
  108. B. Lal, A. K. Kapoor, P. K. Agrawal, O. P. Asthana, and R. C. Srimal, “Role of curcumin in idiopathic inflammatory orbital pseudotumours,” Phytotherapy Research, vol. 14, pp. 443–447, 2000. View at Google Scholar
  109. R. Bundy, A. F. Walker, R. W. Middleton, and J. Booth, “Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study,” Journal of Alternative and Complementary Medicine, vol. 10, no. 6, pp. 1015–1018, 2004. View at Publisher · View at Google Scholar · View at Scopus
  110. S. Durgaprasad, C. G. Pai, Vasanthkumar, J. F. Alvres, and S. Namitha, “A pilot study of the antioxidant effect of curcumin in tropical pancreatitis,” Indian Journal of Medical Research, vol. 122, no. 4, pp. 315–318, 2005. View at Google Scholar · View at Scopus
  111. C. Niederau and E. Göpfert, “The effect of extracts from Schollkraut and Curcuma on upper abdominal pain due to dysfunction of the biliary system: results of a placebo- controlled, double-blind study,” Medizinische Klinik, vol. 94, no. 8, pp. 425–430, 1999. View at Google Scholar · View at Scopus
  112. C. Prucksunand, B. Indrasukhsri, M. Leethochawalit, and K. Hungspreugs, “Phase II clinical trial on effect of the long turmeric (Curcuma longa Linn) on healing of peptic ulcer,” Southeast Asian Journal of Tropical Medicine and Public Health, vol. 32, no. 1, pp. 208–215, 2001. View at Google Scholar · View at Scopus
  113. M. Cruz-Correa, D. A. Shoskes, P. Sanchez et al., “Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis,” Clinical Gastroenterology and Hepatology, vol. 4, no. 8, pp. 1035–1038, 2006. View at Publisher · View at Google Scholar · View at Scopus
  114. R. E. Carroll, R. V. Benya, D. K. Turgeon et al., “Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia,” Cancer Prevention Research, vol. 4, no. 3, pp. 354–364, 2011. View at Publisher · View at Google Scholar · View at Scopus
  115. M. M. Yallapu, M. Jaggi, and S. C. Chauhan, “Curcumin nanoformulations: a future nanomedicine for cancer,” Drug Discovery Today, vol. 17, no. 1-2, pp. 71–80, 2012. View at Google Scholar
  116. Y. Um, S. Cho, H. B. Woo et al., “Synthesis of curcumin mimics with multidrug resistance reversal activities,” Bioorganic and Medicinal Chemistry, vol. 16, no. 7, pp. 3608–3615, 2008. View at Publisher · View at Google Scholar · View at Scopus
  117. V. S. Gota, G. B. Maru, T. G. Soni, T. R. Gandhi, N. Kochar, and M. G. Agarwal, “Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers,” Journal of Agricultural and Food Chemistry, vol. 58, no. 4, pp. 2095–2099, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. S. B. Hanauer and G. Stathopoulos, “Risk-benefit assessment of drugs used in the treatment of inflammatory bowel disease,” Drug Safety, vol. 6, no. 3, pp. 192–219, 1991. View at Google Scholar · View at Scopus
  119. L. Prideaux, M. A. Kamm, P. P. De Cruz, F. K. Chan, and S. C. Ng, “Inflammatory bowel disease in Asia—a systematic review,” Journal of Gastroenterology and Hepatology, vol. 27, no. 8, pp. 1266–1280, 2012. View at Google Scholar
  120. G. M. Holder, J. L. Plummer, and A. J. Ryan, “The metabolism and excretion of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in the rat,” Xenobiotica, vol. 8, no. 12, pp. 761–768, 1978. View at Google Scholar · View at Scopus