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ANTITUMOR, ANTI-INVASION, AND ANTIMETASTATIC EFFECTS OF CURCUMIN

  • Girija Kuttan
  • Kuzhuvelil B. Hari Kumar
  • Chandrasekharan Guruvayoorappan
  • Ramadasan Kuttan
Part of the ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY book series (AEMB, volume 595)

Abstract

Curcumin was found to be cytotoxic in nature to a wide variety of tumor cell lines of different tissue origin. The action of curcumin is dependent on with the cell type, the concentration of curcumin (IC50: 2–40 μg/mL), and the time of the treatment.

Keywords

ANTIMETASTATIC Effect Neck Squamous Cell Carcinoma Cell Human Submandibular Gland Dietary Curcumin Human Melanoma A375 Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    1. Srimal, R. C. and Dhawan B. N. (1973) Pharmacology of diferuloylmethane (curcumin), a non-steroidal anti-inflammatory agent. J. Pharm Pharmacol. 25, 447–452.PubMedGoogle Scholar
  2. 2.
    2. Y. J. Surh, Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 3, 768–780 (2003).PubMedCrossRefGoogle Scholar
  3. 3.
    3. B. B. Aggarwal, A. Kumar, and A. C. Bharti, Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res 23, 363–398 (2003).PubMedGoogle Scholar
  4. 4.
    4. R. K. Maheshwari, A. K. Singh, J. Gaddipati, and R. C. Srimal, Multiple biological activities of curcumin: A short review. Life Sci 78, 2081–2087 (2006).PubMedCrossRefGoogle Scholar
  5. 5.
    5. R. Kuttan, P. Bhanumathy, K. Nirmala, and M. C. George, Potential anticancer activity of turmeric (Curcuma longa). Cancer Lett 29, 197–202 (1985).PubMedCrossRefGoogle Scholar
  6. 6.
    6. K. K. Soudamini. and R. Kuttan, Cytotoxic and tumor reducing properties of curcumin. Indian J Pharmacol 20, 95–101 (1998).Google Scholar
  7. 7.
    7. S. Anuchapreeda, P. Thanarattanakorn, S. Sittipreechacharn, P. Chanarat, and P. Limtrakul, Curcumin inhibits WT1 gene expression in human leukemic K562 cells. Acta Pharmacol Sin 27, 360–366 (2006).PubMedCrossRefGoogle Scholar
  8. 8.
    8. S. Anuchapreeda, P. Limtrakul, P. Thanarattanakorn, S. Sittipreechacharn, and P. Chanarat, Inhibitory effect of curcumin on WT1 gene expression in patient leukemic cells. Arch Pharm Res 29, 80–87 (2006).PubMedCrossRefGoogle Scholar
  9. 9.
    9. L. X. Wu, J. H. Xu, X. W. Huang, K. Z. Zhang, C. X. We, and Y. Z. Chen, Down-regulation of p210(bcr/abl) by curcumin involves disrupting molecular chaperone functions of Hsp90. Acta Pharmacol Sin 27, 694–699 (2006).PubMedCrossRefGoogle Scholar
  10. 10.
    10. S. Chakraborty, U. Ghosh, N. P. Bhattacharyya, R. K. Bhattacharya, and M. Roy, Inhibition of telomerase activity and induction of apoptosis by curcumin in K-562 cells. Mutat Res 596, 81–90 (2006).PubMedGoogle Scholar
  11. 11.
    11. A. Duvoix, F. Morceau, S. Delhalle, M. Schmitz, M., Schnekenburger, M. M. Galteau, M. Dicato, and M. Diederich, Induction of apoptosis by curcumin: mediation by glutathione S-transferase P1-1 inhibition. Biochem Pharmacol 66, 1475–1483 (2003).PubMedCrossRefGoogle Scholar
  12. 12.
    12. A. R. Hussain, M. Al-Rasheed, P. S. Manogaran, K. A. Al-Hussein, L. C. Platanias, K. Al Kuraya, and S. Uddin, Curcumin induces apoptosis via inhibition of PI3′-kinase/AKT pathway in acute T cell leukemias. Apoptosis 11, 245–254 (2006).PubMedCrossRefGoogle Scholar
  13. 13.
    13. J. Rajasingh, H. P. Raikwar, G. Muthian, C. Johnson, and J. J. Bright, Curcumin induces growth-arrest and apoptosis in association with the inhibition of constitutively active JAK-STAT pathway in T cell leukemia. Biochem Biophys Res Commun 340, 359–368 (2006).PubMedCrossRefGoogle Scholar
  14. 14.
    14. 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).PubMedCrossRefGoogle Scholar
  15. 15.
    15. M. Tomita, H. Kawakami, J. N. Uchihara, T. Okudaira, M. Masuda, N. Takasu, T. Matsuda, T. Ohta, Y. Tanaka, K. Ohshiro, and N. Mori, Curcumin (diferuloylmethane) inhibits constitutive active NF-κB, leading to suppression of cell growth of human T-cell leukemia virus type I-infected T-cell lines and primary adult T-cell leukemia cells. Int J Cancer 118, 765–772 (2006).PubMedCrossRefGoogle Scholar
  16. 16.
    16. G. P. Collett and F. C. Campbell, Overexpression of p65/RelA potentiates curcumin-induced apoptosis in HCT116 human colon cancer cells. Carcinogenesis 27, 1285–1291 (2006).PubMedCrossRefGoogle Scholar
  17. 17.
    17. A. Kumar and B. B. Aggarwal, Nuclear factor-kB: Its role in health and disease. J Mol Med 82, 434–438 (2004).PubMedCrossRefGoogle Scholar
  18. 18.
    18. 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).PubMedCrossRefGoogle Scholar
  19. 19.
    19. R. Rashmi, S. Kumar, and D. Karunagaran, Human colon cancer cells lacking Bax resist curcumin-induced apoptosis and Bax requirement is dispensable with ectopic expression of Smac or downregulation of Bcl-XL. Carcinogenesis 26, 713–723 (2005).PubMedCrossRefGoogle Scholar
  20. 20.
    20. D. W. Scott and G. Loo, Curcumin-induced GADD153 gene up-regulation in human colon cancer cells. Carcinogenesis 25, 2155–2164 (2004).PubMedCrossRefGoogle Scholar
  21. 21.
    21. S. Narayan, Curcumin, a multi-functional chemopreventive agent, blocks growth of colon cancer cells by targeting beta-catenin-mediated transactivation and cell-cell adhesion pathways. J Mol Histol 35, 301–307 (2004).PubMedCrossRefGoogle Scholar
  22. 22.
    22. J. Cao, L Jia, H. M. Zhou, Y. Liu, and L. F. Zhong, Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 Cells Toxicol Sci 91, 476–483 (2006).CrossRefGoogle Scholar
  23. 23.
    23. D. W. Seol, Q. Chen, and R. Zarnegar, Transcriptional activation of the hepatocyte growth factor receptor (c-met) gene by its ligand (hepatocyte growth factor) is mediated through AP-1. Oncogene 19, 1132–1137 (2000).PubMedCrossRefGoogle Scholar
  24. 24.
    24. S. H. Jee, S. C. Shen, C. R. Tseng, H. C. Chiu, and M. L. Kuo, Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. J Invest Dermatol 111, 656–661 (1998).PubMedCrossRefGoogle Scholar
  25. 25.
    25. S. Aggarwal, Y. Takada, S. Singh, J. N. Myers, and B. B. Aggarwal, Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-κB signaling. Int J Cancer 111, 679–692 (2004).PubMedCrossRefGoogle Scholar
  26. 26.
    26. C. Ramachandran, S. Rodriguez, R. Ramachandran, P. K. Raveendran Nair, H. Fonseca, Z. Khatib, E. Escalon, and S. J. Melnick, Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines. Anticancer Res 25, 3293–3302 (2005).PubMedGoogle Scholar
  27. 27.
    27. S. Qiu, S. S. Tan, J. A. Zhang, A. Liu, J. Y. Yuan, G. Z. Rao, and W. Y. Wang, Apoptosis induced by curcumin and its effect on c-myc and caspase-3 expressions in human melanoma A375 cell line. Di Yi Jun Yi Da Xue Xue Bao 25, 1517–1521 (2005).PubMedGoogle Scholar
  28. 28.
    28. 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).PubMedCrossRefGoogle Scholar
  29. 29.
    29. M. Zheng, S. Ekmekcioglu, E. T. Walch, C. H. Tang, and E. A. Grimm, Inhibition of nuclear factor-κB and nitric oxide by curcumin induces G2/M cell cycle arrest and apoptosis in human melanoma cells. Melanoma Res 14, 165–171 (2004).PubMedCrossRefGoogle Scholar
  30. 30.
    30. K. Elizabeth and M. N. A. Rao, Effect of curcumin on hydroxyl radical generation through Fenton reaction. Int J Pharm 57, 173–176 (1989).CrossRefGoogle Scholar
  31. 31.
    31. K. Elizabeth and M. N. A. Rao, Oxygen radical scavenging activity of curcumin. Int J Pharm 58, 237–240 (1990).CrossRefGoogle Scholar
  32. 32.
    32. T. Atsumi, K. Tonosaki, and S. Fujisawa, Induction of early apoptosis and ROS-generation activity in human gingival fibroblasts (HGF) and human submandibular gland carcinoma (HSG) cells treated with curcumin. Arch Oral Biol 51, 913–921 (2006).PubMedCrossRefGoogle Scholar
  33. 33.
    33. J. Skommer, D. Wlodkowic, and J. Pelkonen, Cellular foundation of curcumin-induced apoptosis in follicular lymphoma cell lines. Exp Hematol 34, 463–474 (2006).PubMedCrossRefGoogle Scholar
  34. 34.
    34. R. J. Anto, G. Kuttan, and R. Kuttan, Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett 94, 79–83 (1995).CrossRefGoogle Scholar
  35. 35.
    35. R. J. Anto, J. George, K. D. Babu, K. N. Rajasekharan, and R Kuttan, Antimutagenic and anticarcinogenic activity of natural and synthetic curcuminoids. Mutat Res 370, 127–131 (1996).PubMedCrossRefGoogle Scholar
  36. 36.
    36. S. Pal, T. Choudhuri, S. Chattopadhyay, A. Bhattacharya, G. K. Datta, T. Das, and G. Sa, Mechanisms of curcumin-induced apoptosis of Ehrlich's ascites carcinoma cells. Biochem Biophys Res Commun 288, 658–665 (2001).PubMedCrossRefGoogle Scholar
  37. 37.
    37. 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).PubMedCrossRefGoogle Scholar
  38. 38.
    38. M. Churchill, A. Chadburn, R. T. Bilinski, and M. M. Bertagnolli, Inhibition of intestinal tumors by curcumin is associated with changes in the intestinal immune cell profile. J Surg Res 89, 169–175 (2000).PubMedCrossRefGoogle Scholar
  39. 39.
    39. K. K. Soudamini and R. Kuttan, Inhibition of chemical carcinogenesis by curcumin. J Ethnopharmacol 27, 227–233 (1989).PubMedCrossRefGoogle Scholar
  40. 40.
    40. M. T. Huang, Y. R. Lou, W. Ma, H. L. Newmark, R. K. Reuhl, and A. H. Conney, Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon carcinogenesis in mice. Cancer Res 54, 5841–5847 (1994).PubMedGoogle Scholar
  41. 41.
    41. M. Nagabhushan and S.V. Bhide, Curcumin as an inhibitor of cancer. J Am Coll Nutr 11,192–198 (1992).PubMedGoogle Scholar
  42. 42.
    42. M. T. Huang, R. C. Smart, C. Q. Wong, and A. H. Conney, Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 48, 5941–5946 (1988).PubMedGoogle Scholar
  43. 43.
    43. 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).PubMedGoogle Scholar
  44. 44.
    44. A. H. Conney, T. Lysz, T. Ferraro, T. F. Abidi, P. S. Manchand, J. D. Laskin, and M. T. Huang, Inhibitory effect of curcumin and some related dietary compounds on tumor promotion and arachidonic acid metabolism in mouse skin. Adv Enzyme Regul 31, 385–396 (1991).PubMedCrossRefGoogle Scholar
  45. 45.
    45. S. V. Singh, X. Hu, S. K. Srivastava, M. Singh, H. Xia, J. L. Orchard, and H. A. Zaren, Mechanism of inhibition of benzo[a]pyrene-induced forestomach cancer in mice by dietary curcumin. Carcinogenesis 19, 1357–1360 (1998).PubMedCrossRefGoogle Scholar
  46. 46.
    46. 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 14, 2219–2225 (1993).PubMedCrossRefGoogle Scholar
  47. 47.
    47. J. Ushida, S. Sugie, K. Kawabata, Q. V. Pham, T. Tanaka, K. Fujii, H. Takeuchi, Y. Ito, and H. Mori, Chemopreventive effect of curcumin on N-nitroso methyl benzylamine-induced esophageal carcinogenesis in rats. Jpn J Cancer Res 91, 893–898 (2000).PubMedGoogle Scholar
  48. 48.
    48. S. E. Chuang, M. L. Kuo, C. H. Hsu, C. R. Chen, J. K. Lin, G. M. Lai, C. Y. Hsieh, and A. L. Cheng, Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis. Carcinogenesis 21, 331–335 (2000).PubMedCrossRefGoogle Scholar
  49. 49.
    49. K. B. Soni, A. Rajan, and R. Kuttan, Reversal of aflatoxin induced liver damage by turmeric and curcumin. Cancer Lett 66, 115–121 (1992).PubMedCrossRefGoogle Scholar
  50. 50.
    50. A. Sini, R. Kuttan, and G. Kuttan, Immunomodulatory activity of curcumin. Immunol Invest 28, 291–303 (1999).Google Scholar
  51. 51.
    51. V. S. Yadav, K. P. Mishra, D. P. Singh, S. Mehrotra, and V. K. Singh, Immunomodulatory effects of curcumin. Immunopharmacol Immunotoxicol 27, 485–497 (2005).PubMedCrossRefGoogle Scholar
  52. 52.
    52. H. Hidaka, T. Ishiko, T. Furuhashi, H. Kamohara, S. Suzuki, M. Miyazaki, O. Ikeda, S. Mita, T. Setoguchi, and M. Ogawa, Curcumin inhibits interleukin 8 production and enhances interleukin 8 receptor expression on the cell surface: impact on human pancreatic carcinoma cell growth by autocrine regulation. Cancer 95, 1206–1214 (2002).PubMedCrossRefGoogle Scholar
  53. 53.
    53. G. A. Laquerriere, S. C. Gangloff, R. Le Naour, C. Trentesaux, W. Hornebeck, and M. Guenounou, Relative contribution of NF-κB and AP-1 in the modulation by curcumin and pyrrolidine dithiocarbamate of the UVB-induced cytokine expression by keratinocytes. Cytokine 18, 168–177 (2002).CrossRefGoogle Scholar
  54. 54.
    54. B. Y. Kang, S. W. Chung, W. Chung, S. Im, S. Y. Hwang, and T. S. Kim, Inhibition of interleukin-12 production in lipopolysaccharide-activated macrophages by curcumin. Eur J Pharmacol 384, 191–195 (1999).PubMedCrossRefGoogle Scholar
  55. 55.
    55. M. M. Chan, Inhibition of tumor necrosis factor by curcumin, a phytochemical. Biochem Pharmacol 49, 1551–1556n (1995).PubMedCrossRefGoogle Scholar
  56. 56.
    56. L. A. Liotta, Tumor invasion and metastasis; role of the basement membrane. Am.J.Pathol 117, 339–348 (1984).PubMedGoogle Scholar
  57. 57.
    57. L. A. Liotta, Tumor invasion and metastasis; role of extracellular matrix. Cancer Res 46, 1–7 (1986).PubMedCrossRefGoogle Scholar
  58. 58.
    58. B. E. Bachmeier, C. M. Iancu, M. Jochum, and A. G. Nerlich, Matrix metalloproteinases in cancer: comparison of known and novel aspects of their inhibition as a therapeutic approach. Expert Rev Anticancer Ther 5, 149–163 (2005).PubMedCrossRefGoogle Scholar
  59. 59.
    59. L. G. Menon, R. Kuttan, and G. Kuttan, Inhibition of lung metastasis in mice induced by B16F10 melanoma cells by polyphenolic compounds. Cancer Lett 95, 221–225 (1995).PubMedCrossRefGoogle Scholar
  60. 60.
    60. L. G. Menon, R. Kuttan, and G. Kuttan, Anti-metastatic activity of curcumin and catechin. Cancer Lett 141, 159–165 (1999).PubMedCrossRefGoogle Scholar
  61. 61.
    61. A. Banerji, J. Chakrabarti, A. Mitra, and A. Chatterjee, Effect of curcumin on gelatinase A (MMP-2) activity in B16F10 melanoma cells. Cancer Lett 211, 235–242 (2004).PubMedCrossRefGoogle Scholar
  62. 62.
    62. S. Ray, N. Chattopadhyay, A. Mitra, M. Siddiqi, and A. Chatterjee, Curcumin exhibits antimetastatic properties by modulating integrin receptors, collagenase activity, and expression of Nm23 and E-cadherin. J Environ Pathol Toxicol Oncol 22, 49–58 (2003).PubMedGoogle Scholar
  63. 63.
    63. J. H. Hong, K. S. Ahn, E. Bae, S. S. Jeon, and H. Y. Choi, The effects of curcumin on the invasiveness of prostate cancer in vitro and in vivo. Prostate Cancer Prostatic Dis 9, 147–152 (2006).PubMedCrossRefGoogle Scholar
  64. 64.
    64. 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-κB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res 11, 7490–7498 (2005).PubMedCrossRefGoogle Scholar
  65. 65.
    65. K. W. Lee, J. H. Kim, H. J. Lee, and Y. J. Surh, Curcumin inhibits phorbol ester-induced up-regulation of cyclooxygenase-2 and matrix metalloproteinase-9 by blocking ERK1/2 phosphorylation and NF-κB transcriptional activity in MCF10A human breast epithelial cells. Antioxid Redox Signal 7, 1612–1620 (2005).PubMedCrossRefGoogle Scholar
  66. 66.
    66. S. Philip, A. Bulbule, and G. C. Kundu, Matrix metalloproteinase-2: Mechanism and regulation of NF-κB-mediated activation and its role in cell motility and ECM-invasion. Glycoconj J 21, 429–441 (2004).PubMedCrossRefGoogle Scholar
  67. 67.
    67. N. Frank, J. Knauft, F. Amelung, J. Nair, H. Wesch, and H. Bartsch, No prevention of liver and kidney tumors in Long-Evans Cinnamon rats by dietary curcumin, but inhibition at other sites and of metastases. Mutat Res 523524, 127–135 (2003).PubMedGoogle Scholar

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© Springer 2007

Authors and Affiliations

  • Girija Kuttan
  • Kuzhuvelil B. Hari Kumar
  • Chandrasekharan Guruvayoorappan
  • Ramadasan Kuttan

There are no affiliations available

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