Abstract
Colorectal cancer, the second most frequent diagnosed cancer in the US, causes significant morbidity and mortality in humans. Over the past several years, the molecular and biochemical pathways that influence the development of colon cancer have been extensively characterized. Since the development of colon cancer involves multi-step events, the available drug therapies for colorectal cancer are largely ineffective. The radiotherapy, photodynamic therapy, and chemotherapy are associated with severe side effects and offer no firm expectation for a cure. Thus, there is a constant need for the investigation of other potentially useful options. One of the widely sought approaches is cancer chemoprevention that uses natural agents to reverse or inhibit the malignant transformation of colon cancer cells and to prevent invasion and metastasis. Curcumin (diferuloylmethane), a natural plant product, possesses such chemopreventive activity that targets multiple signalling pathways in the prevention of colon cancer development.
Similar content being viewed by others
References
Aggarwal BB, Kumar A, Bharti AC (2003) Anticancer potential of cur-cumin: Preclinical and clinical studies. Anticancer Res 23: 363–398.
Ahmad N, Feyes DK, Nieminen AL, Agarwal R, Mukhtar H(1997) Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J Nat Cancer Inst 89: 1881–1886.
Barker N, Morin PJ, Clevers H (2000) The Yin-Yang of TCF/β-catenin signalling. Adv Cancer Res 77: 1–24.
Ben-Ze'ev A, Geiger B (1998) Differential molecular interactions of beta-catenin and plakoglobin in adhesion, signalling and cancer. Curr Opin Cell Biol 10: 629–639.
Bodmer BF (1996) The somatic evolution of cancer. The Harveian Oration of 1996. J Roy Coll Phys Lond 31: 82–89.
Bordonaro M, Mariadason JM, Aslam F, Heerdt BG, Augenlicht LH (1999) Butyrate-induced apoptotic cascade in colonic carcinoma cells: modulation of the beta-catenin-Tcf pathway and concordance with effects of sulindac and thrichostatin A but not curcumin. Cell Growth Differ 10: 713–720.
Boxer LM, Dang CV (2001) Translocations involving c-myc and c-myc function. Oncogene 20: 5595–5610.
Brancolini C, Sgorbissa A, Schneider C (1998) Proteolytic processing of the adherens junctions components beta-catenin and gamma-catenin/ plakoglobin during apoptosis. Cell Death Differ 5: 1042–1050.
Breen E, Steel G, Mercurio AM (1995) Role of the E-cadherin– catenin complex in modulating cell–cell and cell–matrix adhesive properties of invasive colon carcinoma cells. Ann Surg Oncol 2: 378–385.
Browne SJ, Williams AC, Hague A, Butt AJ, Paraskeva C (1994) Loss of APC protein expressed by human colonic epithelial cells and the appearance of a specific low-molecular-weight form is associated with apoptosis in vitro. Int J Cancer 59: 56–64.
Browne SJ, MacFarlane M, Cohen GM, Paraskeva C (1998) The adenomatous polyposis coli protein and retinoblastoma protein are cleaved early in apoptosis and are potential substrates for caspases. Cell Death Differ 5: 206–213.
Bush JA, Cheung KJ, Li G (2001) Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8 pathway independent of p53. Exp Cell Res 271: 305–314.
Chainani-Wu N (2003) Safety and anti-inflammatory activity of curcumin: A component of turmeric (Curcuma longa). J Altern Complement Med 9: 161–168.
Chapkin RS, Fan Y, Lupton JR (2000) Effect of diet on colonic-programmed cell death: Molecular mechanism of action. Toxicol Lett 112–113: 411–414.
Chen HW, Huang HC (1998) Effects of curcumin on cell cycle progression and apoptosis in vascular smooth muscle cells. Br J Pharmacol 124: 1029–1040.
Chen S, Guttridge DC, You Z, Zhang Z, Fribley A, Mayo MW, Kitajewski J, Wang C (2001) Wnt-1 signalling inhibits apoptosis by activating beta-catenin/T cell factor-mediated transcription. J Cell Biol 152: 87–96.
Chen YR, Tan TH(1998) Inhibition of the c-Jun N-terminal kinase (JNK) signalling pathway by curcumin. Oncogene 17: 173–178.
Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21(4B), 2895–2900.
Clement MV, Hirpara JL, Chawdhury SH, Pervaiz S (1998) Chemo-preventive agent resveratrol, a natural product derived from grapes, triggers CD95 signalling-dependent apoptosis in human tumour cells. Blood 92: 996–1002.
Fearnhead NS, Britton MP, Bodmer WF (2001) The ABC of APC. Human Mol Genet 10: 721–733.
Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumourigenesis. Cell 61: 759–767.
Fukuda K (1999) Apoptosis-associated cleavage of beta-catenin in human colon cancer and rat hepatoma cells. Int J Biochem Cell Biol 31: 516–529.
Gattardi CJ, Gumbiner BM (2001) How β-catenin interacts with its partners. Curr Biol 11: R792–R794.
Goel A, Boland CR, Chauhan DP (2001) Specific inhibition of cyclooxygenase-2 (COX-2) expression by dietary curcumin in HT-29 human colon cancer cells. Cancer Lett 172: 111–118.
Goss KH, Groden J (2000) Biology of the adenomatous polyposis coli tumour suppressor. J Clin Oncol 18: 1967–1979.
Green DW, Roh H, Pippin JA, Drebin JA (2001) Beta-catenin antisense treatment decreases beta-catenin expression and tumour growth rate in colon carcinoma xenografts. J Surg Res 101: 16–20.
Gumbiner BM (2000) Regulation of cadherin adhesive activity. J Cell Biol 148: 399–404.
Hajra KM, Fearon ER (2002) Cadherin and catenin alterations in human cancer. Genes Chrom Cancer 34: 255–268.
Hao X, Frayling IM, Willcocks TC, Han W, Tomlinson IP, Pignatelli MN, Pretlow TP, Talbot IC (2002) Beta-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis. Virchows Arch 440: 362–366.
He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW (1998) Identification of c-MYC as a target of the APC pathway. Science 281: 1509–1512.
Hirohashi S, Kanai Y (2003) Cell adhesion system and human cancer morphogenesis. Cancer Sci 94: 575–581.
Huelsken J, Birchmeier W (2001) New aspects of Wnt signalling pathways in higher vertebrates. Curr Opin Genet Dev 11: 547–553.
Ilyas M, Tomlinson IP, Rowan A, Pignatelli M, Bodmer WF (1997) Beta-catenin mutations in cell lines established from human colorectal cancers. Proc Natl Acad Sci USA 94: 10330–10334.
Inoue M, Suzuki R, Koide T, Sakaguchi N, Ogihara Y, Yabu Y (1994) Antioxidant, gallic acid, induces apoptosis in HL-60RG cells. Biochem Biophys Res Commun 204: 898–904.
Jaiswal AS, Marlow BP, Gupta N, Narayan S (2002) β-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.
Jee SH, Shen SC, Tseng CR, Chiu HC, Kuo ML(1998) Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. J Invest Dermatol 111: 656–661.
Jiang MC, Yang-Yen HF, Yen JJ, Lin JK (1996) Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines. Nutr Cancer 26: 111–120.
Kakar SS, Roy D (1994) Curcumin inhibits TPA induced expression of c-fos, c-jun and c-myc proto-oncogenes messenger RNAs in mouse skin. Cancer Lett 87: 85–89.
Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, Reddy BS (1999) Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res 59: 597–601.
Kelloff GJ, Boone CW, Steele VE, Crowell JA, Lubet R, Sigman CC (1994) Progress in cancer chemoprevention: Perspectives on agent selection and short-term clinical intervention trials. Cancer Res 54(Suppl.) 2015s–2024s.
Kelloff GJ, Crowell JA, Hawk ET, Steele VE, Lubet RA, Boone CW, Covey JM, Doody LA, Omenn GS, Greenwald P, Hong WK, Parkinson DR, Bagheri D, Baxter GT, Blunden M, Doeltz MK, Eisenhauer KM, Johnson K, Knapp GG, Longfellow DG, Malone WF, Nayfield SG, Seifried HE, Swallm LM, Sigman CC (1996) Strategy and planning for chemopreventive drug development: Clinical development plans II. J Cell Biochem 26(Suppl.): 54–71.
Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogelstein B, Clevers H (1997) Constitutive transcriptional activation by a beta-catenin–Tcf complex in APC-/- colon carcinoma. Science 275: 1784–1787.
Korutla L, Cheung JY, Mendelsohn J, Kumar R (1995) Inhibition of ligand-induced activation of epidermal growth factor receptor tyrosine phosphorylation by curcumin. Carcinogenesis 16: 1741–1745.
Kuttan R, Sudheeran PC, Josph CD (1987) Turmeric and curcumin as topical agents in cancer therapy. Tumori 73: 29–31.
Law BK, Waltner-Law ME, Entingh AJ, Chytil A, Aakre ME, Norgaard P, Moses HL (2000) Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen. J Biol Chem 275: 38261–38267.
Limtrakul P, Anuchapreeda S, Lipigoson S, Dunn FW (2001) Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin. BMC Cancer 1: 1–7.
Ling Y, Zhong Y, Perez-Soler R (2001) Disruption of cell adhesion and caspase-mediated proteolysis of beta-and gamma-catenins and APC protein in paclitaxel-induced apoptosis. Mol Pharmacol 59: 593–603.
Mahmoud NN, Carothers AM, Grunberger D, Bilinski RT, Churchill MR, Martucci C, Newmark HL, Bertagnolli MM (2000) Plant phenolics decrease intestinal tumours in an animal model of familial adenomatous polyposis. Carcinogenesis 21: 921–927.
Mann B, Gelos M, Siedow A, Hanski ML, Gratchev A, Ilyas M, Bodmer WF, Moyer MP, Riecken EO, Buhr HJ, Hanski C (1999) Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signalling in human colorectal carcinomas. Proc Natl Acad Sci USA 96: 1603–1608.
Manson MM, Gescher A, Hudson EA, Plummer SM, Squires MS, Prigent SA (2000) Blocking and suppressing mechanisms of chemo-prevention by dietary constituents. Toxicol Lett 112–113: 499–505.
McCarty MF(2001) Current prospects for controlling cancer growth with non-cytotoxic agents–nutrients, phytochemicals, herbal extracts, and available drugs. Med Hypoth 56: 137–154.
Mohan R, Sivak J, Ashton P, Russo LA, Pham BQ, Kasahara N, Raizman MB, Fini ME (2000) Curcuminoids inhibit the angiogenic response stimulated by fibroblast growth factor-2, including expression of matrix metalloproteinase gelatinase B. J Biol Chem 275: 10405–10412.
Moragoda L, Jaczewski R, Majumdar AP(2001) Curcumin induced mod-ulation of cell cycle and apoptosis in gastric and colon cancer cells. Anticancer Res 21(2a): 873–878.
Muller T, Choidas A, Reichman E, Ullrich A (1999) Phosphorylation and free pool of b-catenin are regulated by tyrosine kinases and tyro-sine phosphatases during epithelial cell migration. J Biol Chem 274: 10173–10183.
Muto T, Bussey HJ, Morson BC (1995) The evolution of cancer of the colon and rectum. Cancer 36: 2251–2270.
Papkoff J (1997) Regulation of complexed and free catenin pools by distinct mechanisms. Differential effects of Wnt-1 and v-Src. J Biol Chem 272: 4536–4543.
Paulsen JE (2000) Modulation by dietary factors in murine FAP models. Toxicol Lett 112–113: 403–409.
Pelengaris S, Khan M, Evan G (2002) C-Myc: More than just a matter of life and death. Nat Rev Cancer 2: 764–776.
Phan TT, See P, Lee ST, Chan SY (2001) Protective effects of curcumin against oxidative damage on skin cells in vitro: Its implication for wound healing. J Trauma 51: 927–931.
Polakis P (2000) Wnt signalling and cancer. Genes Dev 14: 1837–1851.
Rao CV, Rivenson A, Simi B, Reddy BS (1995) Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound in mice. Cancer Res 55: 259–266.
Roh H, Green DW, Boswell CB, Pippin JA, Drebin JA(2001) Suppression of beta-catenin inhibits the neoplastic growth of APC-mutant colon cancer cells. Cancer Res 61: 6563–6568.
Schmeiser K, Grand RJ (1999) The fate of E-and P-cadherin during the early stages of apoptosis. Cell Death Differ 6: 377–386.
Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Pirmohamed M, Marnett LJ, Gescher AJ, Steward WP (2001) Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res 7: 1894–1900.
Singh S, Aggarwal BB (1995) Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem 270: 24995–25000.
Sonoshita M, Takaku K, Sasaki N, Sugimoto Y, Ushikubi F, Narumiya S, Oshima M, Taketo MM (2001) Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc(716) knockout mice. Nat Med 7: 1048–1051.
Srimal RC, Dhawan BN (1973) Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol 25: 447–452.
Steinhusen U, Badock V, Bauer A, Behrens J, Wittman-Liebold B, Dorken B, Bommert K (2000) Apoptosis-induced cleavage of beta-catenin by caspase-3 results in proteolytic fragments with reduced transactivation potential. J Biol Chem 275: 16345–16353.
Steinhusen U, Weiske J, Badock V, Tauber R, Bommert K, Huber O (2001) Cleavage and shedding of E-cadherin after induction of apoptosis. J Biol Chem 276: 4972–4980.
Steinmetz KA, Potter JD (1991) Vegetables, fruit, and cancer. I. Epidemiology. Cancer Cause Control 2: 325–357.
Wadham C, Gamble JR, Vadas MA, Khew-Goodall Y (2003) The protein tyrosine phosphatase Pez is a major phosphatase of adherens junctions and dephosphorylates beta-catenin. Mol Biol Cell 14: 2520–2529.
Williams C, Shattuck-Brandt RL, DuBois RN (1999) The role of COX-2 in intestinal cancer. Ann NY Acad Sci 889: 72–83.
Wu Y, Chen Y, Xu J, Lu L (2002) Anticancer activities of curcumin on human Burkitt's lymphoma. Zhonghua Zhong Liu Za Zhi 24: 348–352.
Yap AS, Brieher WM, Gumbiner BM (1997) Molecular and functional analysis of cadherin-based adherens junctions. Annu Rev Cell Dev Biol 13: 119–146.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Narayan, S. Curcumin, A Multi-Functional Chemopreventive Agent, Blocks Growth of Colon Cancer Cells by Targeting β-Catenin-Mediated Transactivation and Cell–Cell Adhesion Pathways. Histochem J 35, 301–307 (2004). https://doi.org/10.1023/B:HIJO.0000032361.98815.bb
Issue Date:
DOI: https://doi.org/10.1023/B:HIJO.0000032361.98815.bb