Biological and Anticancer Effects of Curcumin

Document Type : Review Article

Authors

1 Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran

2 Associate Professor, Department of Biology, School of Sciences, University of Isfahan AND Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, Isfahan, Iran

3 Associate Professor, Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran

Abstract

Turmeric is the general name for Curcuma Longa, an Indian spice belonging to the ginger family. Due to its various applications as a spice, coloring agent etc., turmeric has been used widely for the treatment of various illnesses such as arthritis, ulcers, jaundice, wounds, fever, trauma and skin diseases. The medicinal properties of turmeric are mainly due to presence of a component in the rhizome termed curcumin. The mechanisms by which curcumin exerts its anticancer effects are discussed in this paper. Curcumin has antioxidant, antibacterial, antifungal, antiviral, anti-inflammatory, antiproliferative, and proapoptotic effects. Especially, it has therapeutic applications against different cancers and could be used as a preventive agent. Curcumin induces anticancer activities by prevention of inflammation and proliferation of cancerous cells. Furthermore, it induces apoptosis and prevents metastasis. 

Keywords

References

  1. Aggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol Sci 2009; 30(2): 85-94.
  2. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: a short review. Life Sci 2006; 78(18): 2081-7.
  3. Jagetia GC, Aggarwal BB. "Spicing up" of the immune system by curcumin. J Clin Immunol 2007; 27(1): 19-35.
  4. Kiuchi F, Goto Y, Sugimoto N, Akao N, Kondo K, Tsuda Y. Nematocidal activity of turmeric: synergistic action of curcuminoids. Chem Pharm Bull (Tokyo) 1993; 41(9): 1640-3.
  5. Pelletier J, Vogel A. Examen chimique de la racine de Curcuma. J Pharm 1815; i: 289-300.
  6. Vogel AJ. Sur la Curcumine. Pharm Chem 1842; 3: 20-7.
  7. Milobedzka J, Kostanecki SV, Lampe V. Zur Kenntnis des Curcumins. Berichte der Deutschen Chemischen. Gesellschaft 1910; 43: 2163-70.
  8. Lampe V, Milobedzka J. Studien über Curcumin. Berichte der deutschen chemischen Gesellschaft 1913; 46(2): 2235-40.
  9. Srinivasan KR. A chromatographic study of the curcuminoids in curcuma Longa, L. Journal of Pharmacy and Pharmacology 1953; 5(1): 448-57.
  10. Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J 2009; 11(3): 495-510.
  11. Tonnesen HH, Karlsen J. Studies on curcumin and curcuminoids. VI. Kinetics of curcumin degradation in aqueous solution. Z Lebensm Unters Forsch 1985; 180(5): 402-4.
  12. Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer 2005; 41(13): 1955-68.
  13. Singh S. From exotic spice to modern drug? Cell 2007; 130(5): 765-8.
  14. Aggarwal BB, Harikumar KB. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 2009; 41(1): 40-59.
  15. Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 2003; 23(1A): 363-98.
  16. Shishodia S, Sethi G, Aggarwal BB. Curcumin: getting back to the roots. Ann N Y Acad Sci 2005; 1056: 206-17.
  17. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 2005; 280(7): 5892-901.
  18. Zhang L, Fiala M, Cashman J, Sayre J, Espinosa A, Mahanian M, et al. Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients. J Alzheimers Dis 2006; 10(1): 1-7.
  19. Puglielli L, Tanzi RE, Kovacs DM. Alzheimer's disease: the cholesterol connection. Nat Neurosci 2003; 6(4): 345-51.
  20. Park SY, Kim DS. Discovery of natural products from Curcuma longa that protect cells from beta-amyloid insult: a drug discovery effort against Alzheimer's disease. J Nat Prod 2002; 65(9): 1227-31.
  21. Kim GY, Kim KH, Lee SH, Yoon MS, Lee HJ, Moon DO, et al. Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and translocation of NF-kappa B as potential targets. J Immunol 2005; 174(12): 8116-24.
  22. Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, et al. Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging 2001; 22(6): 993-1005.
  23. Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL. A potential role of the curry spice curcumin in Alzheimer's disease. Curr Alzheimer Res 2005; 2(2): 131-6.
  24. Zhou H, Beevers CS, Huang S. The targets of curcumin. Curr Drug Targets 2011; 12(3): 332-47.
  25. Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer Lett 2008; 267(1): 133-64.
  26. Boon H, Wong J. Botanical medicine and cancer: a review of the safety and efficacy. Expert Opin Pharmacother 2004; 5(12): 2485-501.
  27. Wargovich MJ. Nutrition and cancer: the herbal revolution. Curr Opin Clin Nutr Metab Care 1999; 2(5): 421-4.
  28. Sa G, Das T. Anti cancer effects of curcumin: cycle of life and death. Cell Div 2008; 3: 14.
  29. Sarkar FH, Li Y, Wang Z, Padhye S. Lesson learned from nature for the development of novel anti-cancer agents: implication of isoflavone, curcumin, and their synthetic analogs. Curr Pharm Des 2010; 16(16): 1801-12.
  30. Toda S, Miyase T, Arichi H, Tanizawa H, Takino Y. Natural antioxidants. III. Antioxidative components isolated from rhizome of Curcuma longa L. Chem Pharm Bull (Tokyo) 1985; 33(4): 1725-8.
  31. Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer 2011; 10: 12.
  32. Bengmark S. Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. JPEN J Parenter Enteral Nutr 2006; 30(1): 45-51.
  33. Garodia P, Ichikawa H, Malani N, Sethi G, Aggarwal BB. From ancient medicine to modern medicine: ayurvedic concepts of health and their role in inflammation and cancer. J Soc Integr Oncol 2007; 5(1): 25-37.
  34. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008; 9(1): 46-56.
  35. Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 1999; 18(49): 6853-66.
  36. Luo JL, Kamata H, Karin M. IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy. J Clin Invest 2005; 115(10): 2625-32.
  37. Solt LA, May MJ. The IkappaB kinase complex: master regulator of NF-kappaB signaling. Immunol Res 2008; 42(1-3): 3-18.
  38. Epstein J, Sanderson IR, Macdonald TT. Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies. Br J Nutr 2010; 103(11): 1545-57.
  39. Oyagbemi AA, Saba AB, Ibraheem AO. Curcumin: from food spice to cancer prevention. Asian Pac J Cancer Prev 2009; 10(6): 963-7.
  40. Delston RB, Harbour JW. Rb at the interface between cell cycle and apoptotic decisions. Curr Mol Med 2006; 6(7): 713-8.
  41. Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev 1993; 7(3): 331-42.
  42. Canepa ET, Scassa ME, Ceruti JM, Marazita MC, Carcagno AL, Sirkin PF, et al. INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions. IUBMB Life 2007; 59(7): 419-26.
  43. Yu Q, Geng Y, Sicinski P. Specific protection against breast cancers by cyclin D1 ablation. Nature 2001; 411(6841): 1017-21.
  44. Park MJ, Kim EH, Park IC, Lee HC, Woo SH, Lee JY, 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 2002; 21(2): 379-83.
  45. Srivastava RK, Chen Q, Siddiqui I, Sarva K, Shankar S. Linkage of curcumin-induced cell cycle arrest and apoptosis by cyclin-dependent kinase inhibitor p21(/WAF1/CIP1). Cell Cycle 2007; 6(23): 2953-61.
  46. Hengartner MO. The biochemistry of apoptosis. Nature 2000; 407(6805): 770-6.
  47. Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol 1980; 68: 251-306.
  48. Pongrakhananon V, Rojanasakul Y. Anticancer Properties of Curcumin. In: Gali-Muhtasib H, editor. Advances in Cancer Therapy.Rijeka, Croatia: InTech; 2011. p. 345-68.
  49. Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res 2007; 67(8): 3853-61.
  50. Reuter S, Eifes S, Dicato M, Aggarwal BB, Diederich M. Modulation of anti-apoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells. Biochem Pharmacol 2008; 76(11): 1340-51.
  51. Thayyullathil F, Chathoth S, Hago A, Patel M, Galadari S. Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells. Free Radic Biol Med 2008; 45(10): 1403-12.
  52. Lu HF, Lai KC, Hsu SC, Lin HJ, Yang MD, Chen YL, et al. Curcumin induces apoptosis through FAS and FADD, in caspase-3-dependent and -independent pathways in the N18 mouse-rat hybrid retina ganglion cells. Oncol Rep 2009; 22(1): 97-104.
  53. Anto RJ, Mukhopadhyay A, Denning K, Aggarwal BB. 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 2002; 23(1): 143-50.
  54. Cao Y, Liu Q. Therapeutic targets of multiple angiogenic factors for the treatment of cancer and metastasis. Adv Cancer Res 2007; 97: 203-24.
  55. Barrascout E, Medioni J, Scotte F, Ayllon J, Mejean A, Cuenod CA, et al. [Angiogenesis inhibition: review of the activity of sorafenib, sunitinib and bevacizumab]. Bull Cancer 2010; 97: 29-43.
  56. Yoysungnoen P, Wirachwong P, Bhattarakosol P, Niimi H, Patumraj S. Effects of curcumin on tumor angiogenesis and biomarkers, COX-2 and VEGF, in hepatocellular carcinoma cell-implanted nude mice. Clin Hemorheol Microcirc 2006; 34(1-2): 109-15.
  57. Bae MK, Kim SH, Jeong JW, Lee YM, Kim HS, Kim SR, et al. Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1. Oncol Rep 2006; 15(6): 1557-62.
  58. Bhandarkar SS, Arbiser JL. Curcumin as an inhibitor of angiogenesis. Adv Exp Med Biol 2007; 595: 185-95.
  59. Ray S, Chattopadhyay N, Mitra A, Siddiqi M, Chatterjee A. Curcumin exhibits antimetastatic properties by modulating integrin receptors, collagenase activity, and expression of Nm23 and E-cadherin. J Environ Pathol Toxicol Oncol 2003; 22(1): 49-58.
  60. Hossain DM, Bhattacharyya S, Das T, Sa G. Curcumin: the multi-targeted therapy for cancer regression. Front Biosci (Schol Ed) 2012; 4: 335-55.
  61. Ireson CR, Jones DJ, Orr S, Coughtrie MW, Boocock DJ, Williams ML, et al. Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev 2002; 11(1): 105-11.
  62. Grynkiewicz G, Slifirski P. Curcumin and curcuminoids in quest for medicinal status. Acta Biochim Pol 2012; 59(2): 201-12.
  63. Del Prete A, Scalera A, Iadevaia MD, Miranda A, Zulli C, Gaeta L, et al. Herbal products: benefits, limits, and applications in chronic liver disease. Evid Based Complement Alternat Med 2012; 2012: 837939.
  64. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm 2007; 4(6): 807-18.
  65. Shehzad A, Wahid F, Lee YS. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm (Weinheim) 2010; 343(9): 489-99.
  66. Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK. Curcumin-phospholipid complex: Preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm 2007; 330(1-2): 155-63.
  67. Tsai YM, Jan WC, Chien CF, Lee WC, Lin LC, Tsai TH. Optimised nano-formulation on the bioavailability of hydrophobic polyphenol, curcumin, in freely-moving rats. Food Chemistry 2011; 127(3): 918-25.
  68. Mimeault M, Batra SK. Potential applications of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy. Chin Med 2011; 6: 31.
  69. Liddle M, Hull C, Liu C, Powell D. Contact urticaria from curcumin. Dermatitis 2006; 17(4): 196-7.
  70. Kiec-Swierczynska M, Krecisz B. Occupational allergic contact dermatitis due to curcumin food colour in a pasta factory worker. Contact Dermatitis 1998; 39(1): 30-1.
  71. Van Dau N, Ham NN, Khac DH, Lam NT, Son PT, Tan NT, et al. The effects of a traditional drug, turmeric (Curcuma longa), and placebo on the healing of duodenal ulcer. Phytomedicine 1998; 5(1): 29-34.
  72. Rasyid A, Lelo A. The effect of curcumin and placebo on human gall-bladder function: an ultrasound study. Aliment Pharmacol Ther 1999; 13(2): 245-9.
Journal of Isfahan Medical School
Volume 31, Issue 265 - Serial Number 265
November and December 2014
Pages 2097-2112

Files

History

  • Receive Date: 11 August 2013
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics