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  • Original Paper
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β-Catenin-mediated transactivation and cell–cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells

Oncogene volume 21, pages 8414–8427 (2002)Cite this article

Abstract

The development of nontoxic natural agents with chemopreventive activity against colon cancer is the focus of investigation in many laboratories. Curcumin (feruylmethane), a natural plant product, possesses such chemopreventive activity, but the mechanisms by which it prevents cancer growth are not well understood. In the present study, we examined the mechanisms by which curcumin treatment affects the growth of colon cancer cells in vitro. Results showed that curcumin treatment causes p53- and p21-independent G2/M phase arrest and apoptosis in HCT-116(p53+/+), HCT-116(p53−/−) and HCT-116(p21−/−) cell lines. We further investigated the association of the β-catenin-mediated c-Myc expression and the cell–cell adhesion pathways in curcumin-induced G2/M arrest and apoptosis in HCT-116 cells. Results described a caspase-3-mediated cleavage of β-catenin, decreased transactivation of β-catenin/Tcf-Lef, decreased promoter DNA binding activity of the β-catenin/Tcf-Lef complex, and decreased levels of c-Myc protein. These activities were linked with decreased Cdc2/cyclin B1 kinase activity, a function of the G2/M phase arrest. The decreased transactivation of β-catenin in curcumin-treated HCT-116 cells was unpreventable by caspase-3 inhibitor Z-DEVD-fmk, even though the curcumin-induced cleavage of β-catenin was blocked in Z-DEVD-fmk pretreated cells. The curcumin treatment also induced caspase-3-mediated degradation of cell–cell adhesion proteins β-catenin, E-cadherin and APC, which were linked with apoptosis, and this degradation was prevented with the caspase-3 inhibitor. Our results suggest that curcumin treatment impairs both Wnt signaling and cell–cell adhesion pathways, resulting in G2/M phase arrest and apoptosis in HCT-116 cells.

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References

  • Ahmad N, Feyes DK, Nieminen AL, Agarwal R, Mukhtar H . 1997 J. Natl. Cancer Inst. 89: 1881–1886

  • Ben-Ze'ev A, Geiger B . 1998 Curr. Opin. Cell. Biol. 10: 629–639

  • Bordonaro M, Mariadason JM, Aslam F, Heerdt BC, Augenlicht LH . 1999 Cell Growth Differ. 10: 713–720

  • Boxer LM, Dang CV . 2001 Oncogene 20: 5595–5610

  • Brancolini C, Sgorbissa A, Schneider C . 1998 Cell Death Differ. 5: 1042–1050

  • Browne SJ, Williams AC, Hague A, Butt AJ, Paraskeva C . 1994 Int. J. Cancer 59: 56–64

  • Browne SJ, MacFarlane M, Cohen GM, Paraskeva C . 1998 Cell Death Differ. 5: 206–213

  • Bunz F, Hwang PM, Torrance C, Waldman T, Zhang Y, Dillehay L, Williams J, Lengauer C, Kinzler KW, Vogelstein B . 1999 J. Clin. Invest. 104: 263–269

  • Bush JA, Cheung Jr KJ, Li G . 2001 Oncogene 20: 7597–7609

  • Chan TA, Hwang PM, Hermeking H, Kinzler KW, Vogelstein B . 2000 Genes Dev. 14: 1584–1588

  • Chen S, Guttridge DC, You Z, Zhang Z, Fribley A, Mayo MW, Kitajewski J, Wang C . 2001 J. Cell Biol. 152: 87–96

  • Citro G, d'Agano I, Leonetti C, Perini R, Bucci B, Zon G, Calabretta B, Zupi G . 1998 Cancer Res. 58: 283–289

  • Clement MV, Hirpa JL, Chawdhury SH, Pervaiz S . 1998 Blood 92: 996–1002

  • Daniels DL, Spink KE, Weis WI . 2001 Trends Biochem. Sci. 26: 672–678

  • Fearnhead NS, Britton MP, Bodmer WF . 2001 Hum. Mol. Genet. 10: 721–733

  • Frisch SM, Francis H . 1994 J. Cell Biol. 124: 619–626

  • Goel A, Boland CR, Chauhan DP . 2001 Cancer Lett. 172: 111–118

  • Goss KH, Groden J . 2000 J. Clin. Oncol. 18: 1967–1979

  • Gumbiner BM . 2000 J. Cell. Biol. 148: 399–404

  • He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW . 1998 Science 281: 1509–1512

  • Heatwole VM . 1999 Methods Mol. Biol. 115: 141–148

  • Huang MT, Newmark HL, Frenkel K . 1997 J. Cell. Biochem. 27: Suppl 26–34

  • Huelsken J, Birchmeier W . 2001 Curr. Opin. Genet. Dev. 11: 547–553

  • Ilyas M, Tomlinson IPM, Rowan A, Pignatelli M, Bodmer WF . 1997 Proc. Natl. Acad. Sci. USA 94: 10330–10334

  • Inoue M, Suzuki R, Koide T, Sakaguchi N, Ogihara Y, Yabu Y . 1994 Biochem. Biophys. Res. Commun. 204: 898–904

  • Jaiswal AS, Narayan S . 2001 J. Biol. Chem. 276: 18193–18199

  • Jee SH, Shen SC, Tseng CR, Chiu HC, Kuo ML . 1998 J. Invest. Dermatol. 111: 656–661

  • Jiang MC, Yang-Yen HF, Yen JJ, Lin JK . 1996 Nutr. Cancer 26: 111–120

  • Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, Reddy BS . 1999 Cancer Res. 59: 597–601

  • Kelloff GJ, Boone CW, Steele VE, Crowell JA, Lubet R, Sigman CC . 1994 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 J. Cell Biochem. 26: Suppl 54–71

  • Kim K, Pang KM, Evans M, Hay ED . 2000 Mol Biol. Cell. 11: 3509–3523

  • Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW, Vogenstein B, Clevers H . 1997 Science 275: 1784–1787

  • Kuttan R, Sudheeran PC, Josph CD . 1987 Tumori 73: 29–31

  • Law BK, Waltner-Law ME, Entingh AJ, Chytil A, Aakre ME, Norgaard P, Moses HL . 2000 J. Biol. Chem. 275: 38261–38267

  • Ling Y, Zhong Y, Perez-Soler R . 2001 Mol. Pharmacol. 59: 593–603

  • Mahmoud NN, Carothers AM, Grunberger D, Bilinski RT, Churchill MR, Martucci C, Newmark HL, Bertagnolli MM . 2000 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 Proc. Natl. Acad. Sci. USA 96: 1603–1608

  • Manson MM, Gescher A, Hudson EA, Plummer SM, Squires MS, Prigent SA . 2000 Toxicol. Lett. 112–113: 499–505

  • McCarty MF . 2001 Med. Hypotheses 56: 137–154

  • Meredith Jr JE, Fazeli B, Schwartz MA . 1993 Mol. Biol. Cell 4: 953–961

  • Moragoda L, Jaszewski R, Majumdar AP . 2001 Anticancer Res. 21: 873–878

  • Mukhopadhyay A, Bueso-Ramos C, Chaterjee D, Pantazis P, Agarwal BB . 2001 Oncogene 20: 7597–7609

  • Narayan S, Jaiswal AS . 1997 J. Biol. Chem. 272: 30619–30622

  • Narayan S, Jaiswal AS, Multani AS, Pathak S . 2001 Br. J. Cancer 85: 898–901

  • Obaya AJ, Mateyak MK, Sedivy JM . 1999 Oncogene 18: 2934–2941

  • O'Connell MJ, Walworth NC, Carr AM . 2000 Trends Cell Biol. 10: 296–303

  • Papkoff J . 1997 J. Biol. Chem. 272: 4536–4543

  • Pawlak G, Helfman DM . 2001 Curr. Opin. Genet. Dev. 11: 41–47

  • Pereira MA . 1999 Adv. Exp. Med. Biol. 470: 55–63

  • Phan TT, See P, Lee ST, Chan SY . 2001 J. Trauma 51: 927–931

  • Pines J, Hunter T . 1994 EMBO J. 13: 3772–3781

  • Polakis P . 2000 Genes Dev. 14: 1837–1851

  • Rao CV, Rivenson A, Simi B, Reddy BS . 1995 Cancer Res. 55: 259–266

  • Re F, Zanetti A, Sironi M, Polentarutti N, Lanfrancone L, Dejana E, Colotta F . 1994 J. Cell Biol. 127: 537–546

  • Schmeiser K, Grand RJ . 1999 Cell Death Differ. 6: 377–386

  • Schuler M, Green DR . 2001 Biochem. Soc. Trans. 29: 684–688

  • Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Pirmohamed M, Marnett LJ, Gescher AJ, Steward WP . 2001 Clin. Cancer Res. 7: 1894–1900

  • Singh S, Aggarwal BB . 1995 J. Biol. Chem. 270: 24995–25000

  • Soldani C, Scovassi AI . 2002 Apoptosis 7: 321–328

  • Sonoshita M, Takaku K, Sasaki N, Sugimoto Y, Ushikubi F, Narumiya S, Oshima M, Taketo MM . 2001 Nat. Med. 7: 1048–1051

  • Steinhusen U, Badock V, Bauer A, Behrens J, Wittman-Liebold B, Dorken B, Bommert K . 2000 J. Biol. Chem. 275: 16345–16353

  • Steinhusen U, Weiske J, Badock V, Tauber R, Bommert K, Huber O . 2001 J. Biol. Chem. 276: 4972–4980

  • Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM . 1995 Cell 81: 801–809

  • Thornberry NA, Lazebnik Y . 1998 Science 281: 1312–1316

  • Vindelov LL, Christensen IJ . 1990 Cytometry 11: 753–770

  • Waldman T, Zhang Y, Dillehay L, Yu J, Kinzler K, Vogelstein B, Williams J . 1997 Nat. Med. 3: 1034–1036

  • Wargovich MJ . 1997 Cancer Lett. 114: 11–17

  • Williams C, Shattuck-Brandt RL, DuBois RN . 1999 Ann. NY Acad. Sci. 889: 72–83

  • Yap AS, Brieher WM, Gumbiner BM . 1997 Annu. Rev. Cell. Dev. Biol. 13: 119–146

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Acknowledgements

We would like to thank Dr Bert Vogelstein from the Johns Hopkins Oncology Center (Baltimore, MD, USA) for providing HCT-116(p53+/+), HCT-116(p53−/−) and HCT-116(p21−/−) cell lines and β-catenin/Tcf-Lef responsive plasmids (pTOP-FLASH, pFOP-FLASH); Dr William A Dunn from the Department of Anatomy and Cell Biology, University of Florida (Gainesville, FL, USA), for providing the N-acetyl-leucyl-leucyl-methional (ALLm), N-acetyl-leucyl-leucyl-norleucinal (ALLn), leupeptin and 3-methyladenine (3-MA), Dr Lei Zhou and Dr Lei Xiao, UF Shands Cancer Center, University of Florida (Gainesville, FL, USA) for providing reagents for TUNEL assay and anti-PARP-1 antibody, respectively. We also thank Jessica A Salinas for technical assistance and Rebecca Berg for editorial comments. The FACS analysis was performed in the FCC Laboratory of the ICBR of the University of Florida. These studies were supported in part by the grants awarded to S Narayan from the National Cancer Institute, NIH (CA77721); the 2001-Research Opportunity Fund by the University of Florida (Gainesville, FL, USA) and the 2001-Ralph E Powe Junior Faculty Enhancement Award by the Oak Ridge Associated Universities (Oak Ridge, TN, USA).

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  1. Department of Anatomy and Cell Biology, College of Medicine, The University of Florida, Gainesville, 32610, Florida, FL, USA

    Aruna S Jaiswal, Benjamin P Marlow, Nirupama Gupta & Satya Narayan

  2. UF Shands Cancer Center, College of Medicine, The University of Florida, Gainesville, 32610, Florida, FL, USA

    Aruna S Jaiswal, Benjamin P Marlow, Nirupama Gupta & Satya Narayan

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Correspondence to Satya Narayan.

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Jaiswal, A., Marlow, B., Gupta, N. et al. 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 (2002). https://doi.org/10.1038/sj.onc.1205947

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