Skip to main content

Advertisement

SpringerLink
Log in

Curcumin Alone and in Combination for Prevention of Colorectal Cancer

  • Prevention and Early Detection (N Arber, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

Colorectal cancer (CRC) is a major health concern. It is the third most common type of cancer and cause of death by cancer. Chemoprevention is a promising approach for reducing morbidity and mortality from CRC. The search for a chemoprevention agent with mild side effects has led to particular interest in curcumin. In-vitro and in-vivo studies indicate that curcumin can interfere with multiple cell signaling pathways involved in carcinogenesis, including inhibition of cell cycle progression, induction of apoptosis, slowing of proliferation, and reduction of angiogenesis, invasion, and metastasis formation. Curcumin is also a very potent anti-inflammatory agent and anti-oxidative agent. Curcumin has no adverse effects on normal cells, making it a very promising chemopreventive agent.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. American cancer society. Global cancer facts & figures 2011–2013. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-028323.pdf

  2. Arber N. Cyclooxygenase-2 inhibitors in colorectal cancer prevention: point. Cancer Epidemiol Biomarkers Prev. 2008;17:1852–7.

    Article  CAS  PubMed  Google Scholar 

  3. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  4. Baron JA, Sandler RS, Bresalier RS, et al. APPROVe Trial Investigators. A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology. 2006;131:1674–82.

    Article  CAS  PubMed  Google Scholar 

  5. Bertagnolli MM, Eagle CJ, Zauber AG, et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006;355:873–84.

    Article  CAS  PubMed  Google Scholar 

  6. Arber N, Eagle CJ, Spicak J, et al. Celecoxib for prevention of colorectal adenomas. N Engl J Med. 2006;355:885–95.

    Article  CAS  PubMed  Google Scholar 

  7. Lev-Ari S, Strier L, Kazanov D, et al. Celecoxib and curcumin synergistically inhibit the growth of colorectal cancer cells. Clin Cancer Res. 2005;11:6738–44.

    Article  CAS  PubMed  Google Scholar 

  8. Anand P, Kunnumakkara AB, Newman RA, Aggarwai BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4:807–18.

    Article  CAS  PubMed  Google Scholar 

  9. Prasad S and Aggarwal BB. Herbal medicine: biomolecular and clinical aspects, 2nd edn. CRC press 2011.

  10. Rao CV, Kawamori T, Hamid R, Reddy BS. Chemoprevention of colonic aberrant crypt foci by an inducible nitric oxide synthase-selective inhibitor. Carcinogenesis. 1999;20:641–4.

    Article  CAS  PubMed  Google Scholar 

  11. Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003;23:363–98.

    CAS  PubMed  Google Scholar 

  12. Rao CV, Rivenson A, Simi B, Reddy BS. Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res. 1995;55:259–66.

    CAS  PubMed  Google Scholar 

  13. Kawamori T, Lubet R, Steele VE, et al. Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer res 1999; 59:597–601.

  14. Mukhopadhyay A, Banerjee S, Stafford LJ, Xia C, Liu M, Aggarwal BB. Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation. Oncogene. 2002;21:8852–61.

    Article  CAS  PubMed  Google Scholar 

  15. Aggrawal BB, Banerjee S, Bharadwaj U, Sung B, Shishodia SG. Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines. Biochem Pharmacol. 2007;73:1024–32.

    Article  Google Scholar 

  16. Moos PJ, Edes K, Mullally JE, Fitzpatrick FA. Curcumin impairs tumor suppressor p53 function in colon cancer. Carcinogenesis. 2004;25:1611–7.

    Article  CAS  PubMed  Google Scholar 

  17. He ZY, Shi CB, Wen H, Li FL, Wang J. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest. 2011;29:208–13.

    Article  CAS  PubMed  Google Scholar 

  18. Van Erk MJ, Teuling E, Staal YC, et al. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells. J Carcinog. 2004;12:8.

    Article  Google Scholar 

  19. Goel A, Boland CR, Chauhan DP. Specific inhibition of cyclooxygenase-2 (COX-2) expression by dietary curcumin in HT-29 human colon cancer cells. Cancer Lett. 2001;172:111–8.

    Article  CAS  PubMed  Google Scholar 

  20. Menon VP, Sudheer AR. Antioxidant and anti-inflammatory properties of curcumin. Adv Exp Med Biol. 2007;595:105–25.

    Article  PubMed  Google Scholar 

  21. Beevers CS, Zhou H, Huang S. Hitting the golden TORget: curcumin’s effects on mTOR signaling. Anticancer Agents Med Chem. 2013;13:988–94.

    Article  CAS  PubMed  Google Scholar 

  22. Hong RL, Spohn WH, Hung MC. Curcumin inhibits tyrosine kinase activity of p185neu and also depletes p185neu. Clin Cancer Res. 1999;5:1884–91.

    CAS  PubMed  Google Scholar 

  23. Chen A, Xu J, Johnson AC. 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. 2006;25:278–87.

    PubMed  Google Scholar 

  24. Dhandapani KM, Mahesh VB, Brann DW. Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFkappaB transcription factors. J Neurochem. 2007;102:522–38.

    Article  CAS  PubMed  Google Scholar 

  25. Binion DG, Otterson MF, Rafiee P. Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition. Gut. 2008;57:1509–17.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Kuttan G, Kumar KB, Guruvayoorappan C, Kuttan R. Antitumor, anti-invasion, and anti-metastatic effect of curcumin. Adv Exp Med Biol. 2007;595:173–84.

    Article  PubMed  Google Scholar 

  27. Lin SS, Lai KC, Hsu SC, et al. Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and -9 and vascular endothelial growth factor (VEGF). Cancer Lett. 2009;285:127–33.

    Article  CAS  PubMed  Google Scholar 

  28. Ray S, Chattopadhyay N, Mitra A, Siddigi M, Chatterjee A. Curcumin exhibits antimetastatic properties by modulating integrin receptors, collagenase activity, and expression of Nm23 and E-cadherin. J Environ Toxicol Oncol. 2003;22:49–58.

    CAS  Google Scholar 

  29. Killian PH, Kronski E, Michalik KM, et al. Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2. Carcinogenesis. 2012;33:2507–19.

    Article  CAS  PubMed  Google Scholar 

  30. Hong J, Bose M, Ju J, et al. Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase. Carcinogenesis. 2004;25:1671–9.

    Article  CAS  PubMed  Google Scholar 

  31. Plummer SM, Holloway KA, Manson MM, et al. 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. 1999;18:6013–20.

    Article  CAS  PubMed  Google Scholar 

  32. Brouet I, Ohshima H. Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. Biochem Biophys Res Commun. 1995;206:533–40.

    Article  CAS  PubMed  Google Scholar 

  33. Nanji AA, Jokelainen K, Tipoe GL, Rahemtulla A, Thomas P, Dannenberg AJ. Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-kappa B-dependent genes. Am J Physiol Gastrointest Liver Physiol. 2003;284:G321–7.

    CAS  PubMed  Google Scholar 

  34. Cho JW, Lee KS, Kim CW. Curcumin attenuates the expression of IL-1beta, IL-6, and TNF-alpha as well as cyclin E in TNF-alpha-treated HaCaT cells; NF-kappaB and MAPKs as potential upstream targets. Int J Mol Med. 2007;19:469–74.

    CAS  PubMed  Google Scholar 

  35. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21:2895–900.

    CAS  PubMed  Google Scholar 

  36. Sharma RA, Euden SA, Platton SL, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res. 2004;10:6847–54.

    Article  CAS  PubMed  Google Scholar 

  37. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008;15:787–809.

    Article  Google Scholar 

  38. Garcea G, Jones DJ, Singh R, et al. Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration. Br J Cancer. 2004;90:1011–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J. 2009;11:495–510.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Collett GP, Campbell FC. Curcumin induces c-jun N-terminal kinase-dependent apoptosis in HCT116 human colon cancer cells. Carcinogenesis. 2004;23:2183–9.

    Article  Google Scholar 

  41. Moussavi M, Assi K, Gomez-Munoz A, Salh B. Curcumin mediates ceramide generation via the de novo pathway in colon cancer cells. Carcinogenesis. 2006;27:1636–44.

    Article  CAS  PubMed  Google Scholar 

  42. Guo LD, Chen XJ, Hu YH, Yu ZJ, Wang D, Liu JZ. Curcumin inhibits proliferation and induces apoptosis of human colorectal cells by activating the mitochondria apoptotic pathway. Phytother Res. 2013;27:422–30.

    Article  CAS  PubMed  Google Scholar 

  43. He ZY, Shi CB, Wen H, Li FL, Wang BL, Wang J. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Invest. 2011;29:208–13. The study is one of the few clinical trials that examined the effect of oral curcumin supplementation on patients with CRC. It showed that use of curcumin can improve their general health and lead to weight gain even without generating a change in caloric intake.

    Article  CAS  PubMed  Google Scholar 

  44. Chauhan DP. Chemotherapeutic potential of curcumin for colorectal cancer. Curr Pharm Des. 2002;8:1695–706.

    Article  CAS  PubMed  Google Scholar 

  45. Johnson SM, Gulhati P, Arrieta I, et al. Curcumin inhibits proliferation of colorectal carcinoma by modulating Akt/mTOR signaling. Anticancer Res. 2009;29:3185–90.

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Beevers CS, Li F, Liu L, Huang S. Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells. Int J Cancer. 2006;119:757–64.

    Article  CAS  PubMed  Google Scholar 

  47. Ho E, Beaver LM, Williams DE, Dashwood RH. Dietary factors and epigenetic regulation for prostate cancer prevention. Adv Nutr. 2011;2:497–510.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Mirza S, Sharma G, Parshad R, Gupta SD, Pandya P, Ralhan R. Expression of DNA methyltransferases in breast cancer patients and to analyze the effect of natural compounds on DNA methyltransferases and associated proteins. J Breast Cancer. 2013;16:23–32.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Link A, Balaguer F, Shen Y, Lozano JJ, Leung HC, Boland CR, et al. Curcumin modulates DNA methylation in colorectal cancer cells. PLoS One. 2013;8:e57709. The study is one of the few clinical trials that examined the effect of oral curcumin supplementation on patients with CRC. It showed that use of curcumin can improve their general health and lead to weight gain even without generating a change in caloric intake.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Chen L, Li WF, Wang HX, et al. Curcumin cytotoxicity is enhanced by PTEN disruption in colorectal cancer cells. World J Gastroenterol. 2013;19:6814–24.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Innocenti F, Liu W, Chen P, Desai AA, Das S, Ratain MJ. Haplotypes of variants in the UDP-glucuronosyltransferase1A9 and 1A1 genes. Pharmacol Genet Genomics. 2005;15:295–301.

    Article  CAS  Google Scholar 

  52. Gupta RA, DuBois RN. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer. 2001;1:11–21.

    Article  CAS  PubMed  Google Scholar 

  53. Arber N, DuBois RN. Nonsteroidal anti-inflammatory drugs and prevention of colorectal cancer. Curr Gastroenterol Rep. 1999;1:441–8.

    Article  CAS  PubMed  Google Scholar 

  54. Solomon SD, McMurray JJ, Pfeffer M, et al. Adenoma Prevention with Celecoxib (APC) Study Investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Eng J Med. 2005;352:1071–80.

    Article  CAS  Google Scholar 

  55. Yasunari T, Bhardwaj A, Potdar P, Aggarwal B. Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene. 2004;23:9247–58.

    Google Scholar 

  56. Aroch I, Kraus S, Naumov I, et al. Chemopreventive effects of Coltect, a novel dietary supplement, alone and in combination with 5-aminosalicylic acid in 1,2-dimethylhydrazine-induced colon cancer in rats. Ther Adv Gastroenterol. 2010;3:281–9. Coltect is a novel dietary supplement containing curcumin, green tea, and selenomethionine. Previous reports have suggested that these agents can prevent colorectal cancer (CRC). The chemopreventive effects demonstrated in the study may be of clinical importance, because this safe dietary supplement–drug combination can be administered as a chemopreventive regimen for treatment of CRC.

    Article  CAS  Google Scholar 

  57. Giladi N, Kazanov D, Shpitz B, Aroch I, Kraus S, Arber N. Curcumin potentiates the pro-apoptotic effects of sulindac sulfone in colorectal cancer. Expert Opin Investig Drugs. 2010;S1:S117–24.

    Article  Google Scholar 

  58. Patel BB, Sengupta R, Qazi S, et al. Curcumin enhances the effects of 5-fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF-1R. Int J Cancer. 2008;122:267–73.

    Article  CAS  PubMed  Google Scholar 

  59. Shakibaei M, Mobasheri A, Lueders C, Busch F, Shayan P, Goel A. Curcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of NF-Kb and Src protein kinase signaling pathways. PLoS One. 2013;8:e57128.

    Article  Google Scholar 

  60. Kunnumankkara AB, Diagaradjane P, Anand P, 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. Int J Cancer. 2009;125:2187–97.

    Article  Google Scholar 

Download references

Compliance with Ethics Guidelines

Conflict of Interest

Nataly Shemesh declares that she has no conflict of interest. Nadir Arber has received royalties from Naveh Pharma and has stock/stock options in BioPro.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. The Integrated Cancer Prevention Center, Tel-Aviv Sourasky Medical Center, 6 Weizmann St, Tel Aviv, 64239, Israel

    Nataly Shemesh & Nadir Arber

  2. The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Nataly Shemesh & Nadir Arber

Authors
  1. Nataly Shemesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nadir Arber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nadir Arber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shemesh, N., Arber, N. Curcumin Alone and in Combination for Prevention of Colorectal Cancer. Curr Colorectal Cancer Rep 10, 62–67 (2014). https://doi.org/10.1007/s11888-013-0207-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11888-013-0207-0

Keywords

Search

Navigation