Skip to main content

Advertisement

SpringerLink
Log in

Is Curcumin a Chemopreventive Agent for Colorectal Cancer?

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

Abstract

Curcumin is the main component of the Indian spice curcuma (Indian saffron), originating from its rhizome. Curcumin is consumed as food, anywhere in the world and almost daily in India. It has also been used as a drug in Ayurvedic medicine for centuries. This polyphenol substance has pleiotropic effects, interfering with many signaling molecules: pro-inflammatory molecules, transcription factors, enzymes, protein kinases, transport proteins, proteins involved in cell survival, adhesion molecules, growth factors, receptors, proteins regulating cell cycle, chemokines, nucleic acids…. Oral bioavailability of traditional forms of curcumin is low, making it particularly suitable for therapy of diseases of the intestinal tract. Curcumin has anti-inflammatory, anti-oxidant, anti-proliferative, and pro-apoptotic properties, making it an excellent candidate as a chemopreventive agent in colorectal cancer. Contrasting with many in vitro studies devoted to curcumin and a lot of in vivo studies on animal models, curcumin has rarely been assessed in clinical studies dealing with digestive oncology. However, several clinical trials are in progress in this domain. Until now, curcumin has no official medical indication.

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

Fig. 1

Similar content being viewed by others

References

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

  1. Prasad S, Tyagi AK, Aggarwal BB. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from the golden spice. Cancer Res Treat. 2014;46:2–18. This review focuses on the means to increase oral bioavailability of curcumin.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Gupta SC, Patchva S, Koh W, Aggarwal BB. Discovery of curcumin, a component of the golden spice, and its miraculous biological activities. Clin Exp Pharmacol Physiol. 2012;39:283–99. Excellent review of the history and the various biological properties of curcumin.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kunnumakkara AB, Guha S, Aggarwal BB. Curcumin and colorectal cancer: add spice to your life. Curr Color Cancer Rep. 2009;5:5–14.

    Article  Google Scholar 

  4. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008;75:787–809. Excellent review summarizing studies focusing on the clinical pharmacokinetics of curcumin.

    Article  CAS  PubMed  Google Scholar 

  5. Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma Longa: a review of preclinical and clinical research. Alternat Med Rev. 2009;14:141–53.

    Google Scholar 

  6. Shoba G, Joy D, Joseph T, et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64:353–6.

    Article  CAS  PubMed  Google Scholar 

  7. Vareed SK, Kakarala M, Ruffin MT, et al. Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev. 2008;17:1411–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sharma RA, McLelland HR, Hill KA, et al. Pharmacodynamic and pharmacokinetic study of oral curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001;7:1894–900.

    CAS  PubMed  Google Scholar 

  9. 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 

  10. Lao CD, Ruffin M, Normolle D, et al. Dose escalation of a curcuminoid formulation. BMC Complement Alternat Med. 2006;6:10.

    Article  Google Scholar 

  11. 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 

  12. Carroll RE, Benya RV, Turgeon DK, et al. Phase IIA clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila). 2011;4:354–64.

    Article  CAS  Google Scholar 

  13. 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  PubMed Central  Google Scholar 

  14. Garcea G, Berry DP, Jones DJ, et al. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev. 2005;1:120–5.

    Google Scholar 

  15. Plummer SM, Hill KA, Festing MF, et al. Clinical development of leucocyte cyclooxygenase 2 activity as a systemic biomarker for cancer chemopreventive agents. Cancer Epidemiol Biomarkers Prev. 2001;10:1295–9.

    CAS  PubMed  Google Scholar 

  16. He ZY, Shi CB, Wen H, et al. Upregulation of p53 expression in patients with colorectal cancer by administration of curcumin. Cancer Investig. 2011;29:208–13.

    Article  CAS  Google Scholar 

  17. Park J, Conteas CN. Anti-carcinogenic properties of curcumin on colorectal cancer. World J Gastrointest Oncol. 2010;2:169–76.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Yadav VR, Aggarwal BB. Curcumin, a component of the golden spice, targets multiple angiogenic pathways. Cancer Biol Ther. 2011;11:236–41. Excellent short review summarizing the various anti-angiogenic effects of curcumin, including inhibition of vasculogenic mimicry, inhibition of MMP-9, inhibition of EphA2 and PI3K and thus tumour growth and angiogenesis.

    Article  CAS  PubMed  Google Scholar 

  19. Patel VB, Misra S, Patel BB, Majumdar APN. Colorectal cancer: chemopreventive role of curcumin and resveratrol. Nutr Cancer. 2010;62:958–67.

    Article  CAS  PubMed  Google Scholar 

  20. Link A, Balaguer F, Shen Y, et al. Curcumin modulates DNA methylation in colorectal cancer cells. PLoS One. 2013;8(2):e57709. doi:10.1371/journal.pone.0057709. Original study assessing the effects of curcumin on DNA methylation, a key target of carcinogenesis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Reuter S, Gupta SC, Park B, et al. Epigenetic changes induced by curcumin and other natural compounds. Genes Nutr. 2011;6:93–108. This review summarizes current knowledge on the effect of curcumin on the regulation of histone deacetylases, histone acetyltransferases, DNA methyltransferase I and microRNAs and how these changes modulate gene expression.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Giladi N, Kazanov D, Shpitz B, et al. Curcumin potentiates the pro-apoptotic effects of sulindac sulfone in colorectal cancer. Curr Opin Investig Drugs. 2010;19 suppl 1:S117–24.

    Article  CAS  Google Scholar 

  23. Shehzad A, Ul Islam S, Lee J, Lee YS. Prostaglandin E2 reverses curcumin-induced inhibition of survival signal pathways in human colorectal carcinoma (HCT-15) cell lines. Mol Cells. 2014;37:899–906.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Shakibaei M, Buhrmann C, Kraehe P, et al. Curcumin chemosensitizes 5 fluoro-uracil resistant MMR deficient human colon cancer cells in high density cultures. PLoS One. 2014;9(1):e85397. doi:10.1371/journal.pone0085397.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Howells LM, Sale S, Sriramareddy SN. Curcumin ameliorates oxaliplatin-induced chemoresistance in HCT116 colorectal cancer cells in vitro and in vivo. Int J Cancer. 2011;129:476–86.

    Article  CAS  PubMed  Google Scholar 

  26. James MI, Iwuji C, Irving G, et al. Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy. Cancer Lett. 2015;364:135–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rao CV, Simi B, Reddy BS, et al. Inhibition by dietary curcumin of azoxymethane-induced ornithine decarboxylase, tyrosine protein kinase, arachidonic acid metabolism and aberrant cryptic foci formation in the rat colon. Carcinogenesis. 1993;11:2219–25.

    Article  Google Scholar 

  28. Huang MT, Lou YR, Ma W, et al. Inhibitory effects of dietary curcumin on forestomach, duodenal and colon carcinogenesis in mice. Cancer Res. 1994;54:5841–7.

    CAS  PubMed  Google Scholar 

  29. Kim JM, Araki S, Kim DJ, et al. Chemopreventive effects of carotenoids and curcumin on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation. Carcinogenesis. 1998;19:81–5.

    Article  CAS  PubMed  Google Scholar 

  30. Rao CV, Rivenson A, Simi B, Reddy BS. Chemoprevention of colon cancer by dietary curcumin. Ann N Y Acad Sci. 1995;768:201–4.

    Article  CAS  PubMed  Google Scholar 

  31. 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. Cancer Res. 1999;59:597–601.

    CAS  PubMed  Google Scholar 

  32. Collett GP, Robson CN, Mathers JC, Campbell JC. Curcumin modifies Apc(min) apoptosis resistance and inhibits 2-amino 1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) induced tumour formation in Apc(min) mice. Carcinogenesis. 2001;22:821–5.

    Article  CAS  PubMed  Google Scholar 

  33. Pereira MA, Grubbs CJ, Barnes LH, et al. Effects of the phytochemicals, curcumin and quercetin, upon azoxymethane-induced colon cancer and 7,12-dimethylbenz[a] anthracen-induced mammary cancer in rats. Carcinogenesis. 1996;17:1305–11.

    Article  CAS  PubMed  Google Scholar 

  34. Kwon Y, Malik M, Magnuson BA. Inhibition of colonic aberrant crypt foci by curcumin in rats is affected by age. Nutr Cancer. 2004;48:37–43.

    Article  CAS  PubMed  Google Scholar 

  35. Shpitz B, Giladi N, Sagiv E, et al. Celecoxib and curcumin additively inhibit the growth of colorectal cancer in a rat model. Digestion. 2006;74:140–4.

    Article  CAS  PubMed  Google Scholar 

  36. Sugimoto K, Hanai H, Tozawa K, et al. Curcumin prevents and ameliorates trinitrobenzene sulfonic acid-induced colitis in mice. Gastroenterology. 2002;123:1912–22.

    Article  CAS  PubMed  Google Scholar 

  37. Salh B, Assi K, Templeman V, et al. Curcumin attenuates DNB-induced murine colitis. Am J Physiol Gastrointest Liver Physiol. 2003;285:G235–43.

    Article  CAS  PubMed  Google Scholar 

  38. Ukil A, Maity S, Karmakar S, et al. Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis. Br J Pharmacol. 2003;139:209–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Venkataranganna MV, Rafiq M, Gopumadhavan S, et al. NCB-02 (standard curcumin preparation) protects dinitrochlorobenzene-induced colitis through down-regulation of NFkappa-B and iNOS. World J Gastroenterol. 2007;13:1103–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Huang MT, Deschner EE, Newmark HL, et al. Effect of dietary curcumin and ascorbyl palmitate on azoxymethanol-induced colonic epithelial cell proliferation and focal areas of dysplasia. Cancer Lett. 1992;64:117–21.

    Article  CAS  PubMed  Google Scholar 

  41. Perkins S, Verschoyle RD, Hill K, et al. Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a model of familial adenomatous polyposis. Cancer Epidemiol Biomarkers Prev. 2002;11:535–40.

    CAS  PubMed  Google Scholar 

  42. Li L, Ahmed B, Mehta K, Kurzrock R. Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer. Mol Cancer Ther. 2007;6:12761282.

    Google Scholar 

  43. Kunnumakkara AB, Diagaradjane P, Guha S, et al. Curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting nuclear factor-kappa B-regulated gene products. Clin Cancer Res. 2008;14:2128–21361.

    Article  CAS  PubMed  Google Scholar 

  44. Byun SY, Kim DB, Kim E. Curcumin ameliorates the tumor-enhancing effects of a high-protein diet in an azoxymethane-induced mouse model of colon carcinogenesis. Nutr Res. 2015;35(8):726–35. doi:10.1016/j.nutres.2015.05.016.

    Article  CAS  PubMed  Google Scholar 

  45. Pettan-Brewer C, Morton J, Mangalindan R. Curcumin suppresses intestinal polyps in APC Min mice fed a high fat diet. Pathobiol Aging Age Relat Dis. 2011. doi:10.3402/pba.v1i0.7013.

    Google Scholar 

  46. Cruz-Correa M, Shoskes DA, Sanchez P. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2006;4:1035–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Pharmacologie, APHP, Hôpital Avicenne, 125 Route de Stalingrad, 93009, Bobigny, France

    Bernard Uzzan

  2. Service de Gastro-entérologie, Hôpital Avicenne, Bobigny, France

    Robert Benamouzig

Authors
  1. Bernard Uzzan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert Benamouzig
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert Benamouzig.

Ethics declarations

Conflict of Interest

The authors declare that they have no competing interests.

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.

Additional information

This article is part of the Topical Collection on Prevention and Early Detection

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Uzzan, B., Benamouzig, R. Is Curcumin a Chemopreventive Agent for Colorectal Cancer?. Curr Colorectal Cancer Rep 12, 35–41 (2016). https://doi.org/10.1007/s11888-016-0307-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11888-016-0307-8

Keywords

Search

Navigation