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Review

Matrix metalloproteinases in cancer: comparison of known and novel aspects of their inhibition as a therapeutic approach

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Pages 149-163 | Published online: 10 Jan 2014

References

  • McLeod HL. Individualized cancer therapy: molecular approaches to the prediction of tumor response. Expert Rev. Anticancer Ther.2, 113–119 (2002).
  • Hanahan D, Weinberg RA. The hallmarks of cancer. Cell100, 57–70 (2000).
  • Hagedorn HG, Bachmeier BE, Nerlich AG. Synthesis and degradation of basement membranes and extracellular matrix and their regulation by TGF-α in invasive carcinomas. Int. J. Oncol.18, 669–681 (2001).
  • DeClerck YA, Mercurio AM, Stack MS et al. Proteases, extracellular matrix and cancer. Am. J. Pathol.164, 1131–1139 (2004).
  • Overall C, Lopez-Otin C. Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nature Rev. Cancer2, 657–672 (2002).
  • Borkakoti N. Matrix metalloprotease inhibitors: design from structure. Biochem. Soc. Trans.32, 17–20 (2004).
  • Baker AH, Edwards DR, Murphy G. Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J. Cell Sci.115, 3719–3727 (2002).
  • Brown PD. Matrix metalloproteinase inhibitors. Angiogenesis1, 142–154 (1997).
  • Ramnath N, Creaven PJ. Matrix metalloproteinase inhibitors. Curr. Oncol. Rep.6, 96–102 (2004).
  • Hojilla CV, Mohammed FF, Khokha R. Matrix metalloproteinases and their tissue inhibitors direct cell fate during cancer development. Br. J. Cancer89, 1817–1821 (2003).
  • Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM. Matrix metalloproteinases: biological activity and clinical implications. J. Clin. Oncol.18, 1135–1149 (2000).
  • Westermarck J, Kähäri VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J.13, 781–792 (1999).
  • Woessner JF. The matrix metalloproteinase family. In: Matrix Metalloproteinases. Parks WC, Meachim RP (Eds), Academic Press, CA, USA. 1–14 (1998).
  • Seltzer JL, Eisen AZ, Bauer EA et al. Cleavage of Type VII collagen by interstitial collagenase and Type IV collagenase (gelatinase) derived from human skin. J. Biol. Chem.164, 3822–3826 (1989).
  • Hasty KA, Jeffrey JJ, Hibbs MS, Welgus HG. The collagen substrate specificity of human neutrophil collagenase. J. Biol. Chem.262, 10048–10052 (1987).
  • Goldberg GI, Wilhelm S, Kronberger A et al. Human fibroblast collagenase. Complete primary structure and homology to an oncogene transformation-induced rat protein. J. Biol. Chem.261, 6600–6605 (1986).
  • Bachmeier BE, Nerlich AG, Boukamp P et al. Human keratinocyte cell lines differ inthe expression of the collagenolytic matrix metalloproteinases-1, -8, and -13 and TIMP-1. Biol. Chem.381, 509–516 (2000).
  • Bode W, Maskos K. Structural basis of the matrix metalloproteinases and their physiological inhibitors, the tissue inhibitors of metalloproteinases. Biol. Chem.384, 863–872 (2003).
  • Barrett AJ, Rawlings ND, Woessner JF. Handbook of Proteolytic Enzymes. Academic Press, London, UK (1998).
  • Yoon SO, Park SJ, Yun CH, Chung AS. Roles of matrix metalloproteinases in tumor metastasis and angiogenesis. J. Biochem. Mol. Biol.36(1), 128–137 (2003).
  • Shapiro SD, Kobayashi DK, Ley TJ. Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J. Biol. Chem.268, 23824–23829 (1993).
  • Shipley JM, Wesselschmidt RL, Kobayashi DK et al. Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. Proc. Natl Acad. Sci. USA93, 3942–3946 (1996).
  • Marchenko GN, Strongin AY. MMP-28, a new human matrix metalloproteinase with an unusual cysteine-switch sequence is widely expressed in tumors. Gene265, 87–93 (2001).
  • Saarialho-Kere U, Kerkela E, Jahkola T et al. Epilysin (MMP-28) expression is associated with cell proliferation during epithelial repair. J. Invest. Dermatol.119, 14–21 (2002).
  • Chakraborti S, Mandal M, Das S et al. Regulation of matrix metalloproteinases: an overview. Mol. Cell. Biochem.253, 269–285 (2003).
  • Bannikov GA, Karelina TV, Collier IE et al. Substrate binding of gelatinase B induces its enzymatic activity in the presence of intact propeptides. J. Biol. Chem.277, 16022–16027 (2002).
  • Overall CM, Tam E, McQuibban GA et al. Domain interactions in the gelatinase A:TIMP-2:MT1-MMP activation complex: the ectodomain of the 44 kDa form of membrane Type 1 matrix metalloproteinase does not modulate gelatinase A activation. J. Biol. Chem.275, 39497–39505 (2000).
  • Deryugina EI, Ratnikov B, Monosov E et al. MT1-MMP initiates activation of pro-MMP-2 and integrin ανα3 promotes maturation of MMP-2 in breast carcinoma cells. Exp. Cell Res.263, 209–223 (2001).
  • Seiki M. Membrane-type matrix metalloproteinases. APMIS107, 137–143 (1999).
  • Basset P, Okada A, Chenard MP et al. Matrix metalloproteinases as stromal effectors of human carcinoma progression: therapeutic implications. Matrix Biol.15, 535–541 (1997).
  • Johnsen M, Lund LR, Romer J, Almholt K, Dano K. Cancer invasion and tissue remodelling: common themes in proteolytic matrix degradation. Curr. Opin. Cell Biol.10, 667–671 (1998).
  • Bachmeier BE, Boukamp P, Lichtinghagen R, Fusenig N, Fink E. Matrix metalloproteinase-2, -3, -7, -9 and -10, but not -11 are differentially expressed in normal, benign and malignant human keratinocyte cell lines. Biol. Chem.381, 497–507 (2000).
  • Bachmeier BE, Nerlich A, Lichtinghagen R, Sommerhoff CP. Matrix metalloproteinases (MMPs) in breast cancer cell lines of different tumorigenicity. Anticancer Res.21, 3821–3828 (2001).
  • Lebeau A, Nerlich AG, Sauer U, Lichtinghagen R, Löhrs U. Tissue distribution of major matrix metalloproteinases and their transcripts in human breast carcinomas. Anticancer Res.19, 4257–4264 (1999).
  • Lebeau A, Müller-Aufdemkamp C, Allmacher C et al. Cellular protein and mRNA expression patterns of matrix metalloproteinases-2, -3 and -9 in human breast cancer: correlation with tumor growth. J. Mol. Histol.35(5),443–455 (2004).
  • Nerlich AG, Lebeau A, Hagedorn HG, Sauer U, Schleicher ED. Morphological aspects of altered basement membrane metabolism in invasive carcinomas of the breast and the larynx. Anticancer Res.18, 3515–3520 (1998).
  • O’Charoenrat P, Rhys-Evans PH, Eccles SA. Expression of matrix metalloproteinases and their inhibitors correlates with invasion and metastasis in squamous cell carcinoma of the head and neck. Arch. Otolaryngol. Head Neck Surg.127, 813–820 (2001).
  • Fundyler O, Khanna M, Smoller BR. Metalloproteinase-2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas. Mod. Pathol.17, 496–502 (2004).
  • Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinase: evolution, structures and function. Biochim. Biophys. Acta1477, 267–283 (2000).
  • Will H, Atkinson SJ, Butler GS, Smith B, Murphy G. The soluble catalytic domain of membrane Type 1 matrix metalloproteinase cleaves the propeptide of progelatinase A and initiates autoproteolytic activation: regulation by TIMP-2 and TIMP-3. J. Biol. Chem.271, 17119–17123 (1996).
  • Amour A, Knight CG, Webster A et al. The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3. FEBS Lett.473, 275–279 (2000).
  • Kashiwagi M, Tortorella M, Nagase H, Brew K. TIMP-3 is a potent inhibitor of aggrecanase 1 (ADAM-TS4) and aggrecanase 2 (ADAM-TS5). J. Biol. Chem.276, 12501–12504 (2001).
  • Yu WH, Yu S, Meng Q, Brew K, Woessner JF. TIMP-3 binds to sulfated glycosaminoglycans of the extracellular matrix. J. Biol. Chem.275, 31226–31232 (2000).
  • Visser R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases. Structure, function and biochemistry. Circ. Res.92, 827–839 (2003).
  • Kahari VM, Saarialho-Kere U. Matrix metalloproteinases and their inhibitors in tumor growth and invasion. Ann. Med.31, 34–45 (1999).
  • Benaud C, Dickson RB, Thompson EW. Roles of matrix metalloproteinases in mammary gland development and cancer. Breast Cancer Res. Treat.50, 97–116 (1998).
  • Höyhtyä M, Fridman R, Komarek D et al. Immunohistochemical localization of matrix metalloproteinase-2 and its specific inhibitor TIMP-2 in neoplastic tissues with monoclonal antibodies. Int. J. Cancer56, 500–505 (1994).
  • Poulsom R, Hanby AM, Pignatelli M et al. Expression of gelatinase A and TIMP-2 mRNAs in desmoplastic fibroblasts in both mammary carcinomas and basal cell carcinomas of the skin. J. Clin. Pathol.46, 429–436 (1993).
  • Lee MH, Maskos K, Knäuper V, Dodds P, Murphy G. Mapping and characterization of the functional epitopes of tissue inhibitor of metalloproteinases (TIMP)-3 using TIMP-1 as the scaffold: a new frontier in TIMP engineering. Protein Sci.11, 2493–2503 (2002).
  • Lee MH, Rapti M, Knäuper V, Murphy G. Threonin 98, the pivotal residue of tissue inhibitor of metalloproteinases (TIMP)-1 in metalloproteinase recognition. J. Biol. Chem.279, 17562–17569 (2004).
  • Grignon DJ, Sakr W, Ravery V et al. High levels of tissue inhibitors of metalloproteinase 2 (TIMP-2) expression are associated with poor outcome in invasive bladder cancer. Cancer Res.56, 1654–1659 (1996).
  • Stetler-Stevenson M, Mansoor A, Lim MS et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs) in reactive and neoplastic lymph nodes. Blood89, 1708–1715 (1997).
  • Brand K, Baker A, Perez-Canto A et al. Treatment of colorectal liver metastases by adenoviral transfer of tissue inhibitor of metalloproteinase-2 into the liver tissue. Cancer Res.60, 5723–5730 (2000).
  • Celiker M, Wang M, Atsidaftos E et al. Inhibition of Wilm’s tumor growth by intramuscular administration of tissue inhibitor of metalloproteinases-4 plasmid DNA. Oncogene20, 4337–4343 (2001).
  • Bergers G, Javaherian K, Lo K, Folkman J, Hanahan D. Effects of angiogenesis inhibitors on multistage carcinogenesis in mice. Science284, 808–812 (1999).
  • Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science295, 2387–2392 (2002).
  • Jiang Y, Wang M, Celiker M et al. Stimulation of mammary tumorigenesis by systemic tissue inhibitor of matrix metalloproteinase-4 gene delivery. Cancer Res.61, 2365–2370 (2001).
  • Barrett AJ. α2-macroglobulin. Methods Enzymol.80, 737–754 (1981).
  • Cawston TE, Mercer E. Preferential binding of collagenase to α2-macroglobulin in the presence of the tissue inhibitor of metalloproteinases. FEBS Lett.209, 9–12 (1986).
  • Bein K, Simons M. Thrombospondin Type 1 repeats interact with matrix metalloproteinase 2. Regulation of metalloproteinase activity. J. Biol. Chem.275, 32167–32173 (2000).
  • Rodriguez-Manzaneque JC, Lane TF, Ortega MA et al. Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor. Proc. Natl Acad. Sci USA98, 12485–12490 (2001).
  • Takahashi C, Sheng Z, Horan T et al. Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. Proc. Natl Acad. Sci. USA95, 13221–13226 (1998).
  • Oh J, Takahasi R, Kondo S et al. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell107, 789–800 (2001).
  • Herman MP, Suhkova GK, Kisiel W et al. Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix metalloproteinases with implications for atherosclerosis. J. Clin. Invest.107, 1117–1126 (2001).
  • Mott JD, Thomas CL, Rosenbach MT et al. Post-translational proteolytic processing of procollagen C-terminal proteinase enhancer releases a metalloproteinase inhibitor. J. Biol. Chem.275, 1384–1390 (2000).
  • Woessner JF Jr. MMPs and TIMPs – an historical perspective. Mol. Biotechnol.22, 333–349 (2002).
  • Beckett RP. Recent advances in the field of matrix metalloproteinase inhibitors. Expert Opin. Ther. Patents6, 1305–1315 (1996).
  • Brown PD, Giavazzi R. Matrix metalloproteinase inhibition: a review of antitumor activity. Ann. Oncol.6, 967–974 (1995).
  • Tremont-Lukas IW, Gilbert MR. Advances in molecular therapies in patients with brain tumors. Cancer Control10, 125–137 (2003).
  • Eskens FALM, Levitt NC, Sparreboom A et al. Effect of food on the pharmacokinetics of oral MMI270B (CGS 27023A), a novel matrix metalloproteinase inhibitor. Clin. Cancer Res.6, 431–434 (2000).
  • Levitt NC, Eskens FALM, O’Byrne KJ et al. Phase I and pharmacological study of the oral matrix metalloproteinase inhibitor MMI270 (CGS 27023A) in patients with advanced solid cancer. Clin. Cancer Res.7, 1912–1922 (2001).
  • Nakamura ES, Kiozumi K, Kobayashi M, Saiki I. Inhibition of lymphangiogenesis-related properties of murine lymphatic endothelial cells and lymph node metastasis of lung cancer by the matrix metalloproteinase inhibitor MMI270. Cancer Sci.95, 23–31 (2004).
  • Sparano JA, Gray R, Giantonio B et al. Evaluating anti-angiogenesis agents in the clinic: the Eastern Co-operative Oncology Group portfolio of clinical trials. Clin. Cancer Res.10, 1206–1211 (2004).
  • Yamamoto H, Adachi Y, Itoh F et al. Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma. Cancer Res.59, 3313–3316 (1999).
  • Murray GI, Duncan ME, O’Neil P et al. Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer. Nature Med.4, 461–462 (1996).
  • Yamamoto H, Itoh F, Iku S et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinoma: clinicopathologic and prognostic significance of matrilysin expression. J. Clin. Oncol.19, 1118–1127 (2001).
  • Shepherd FA, Giaccone G, Seymour L et al. Prospective, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organization for Research and Treatment of Cancer. J. Clin. Oncol.20, 4434–4439 (2002).
  • Bramhall SR, Hallissey MT, Whiting J et al. Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial. Br. J. Cancer86, 1864–1870 (2002).
  • Wall L, Talbot DC, Bradbury P, Jodrell DI. A Phase I and pharmacological study of the matrix metalloproteinase inhibitor BB-3644 in patients with solid tumours. Br. J. Cancer90, 800–804 (2004).
  • Quirt I, Bodurth A, Lohmann R et al. Phase II study of marimastat (BB-2516) in malignant melanoma: clinical and tumor biopsy study of the National Cancer Institute of Canada Clinical Trials Group. Invest. New Drugs20, 431–437 (2002).
  • Larson DA, Prados M, Lamborn KR et al. Phase II study of high central dose gamma knife radiosurgery and marimastat in patients with recurrent malignant glioma. Int. J. Radiat. Biol. Phys.54, 1397–1404 (2002).
  • Maekawa K, Sato H, Furukawa M, Yoshizaki T. Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model. Clin. Exp. Metastasis19, 513–518 (2002).
  • Groves MD, Puduvalli VK, Hess KR et al. Phase II trial of temozolomide plus the matrix metalloproteinase inhibitor marimastat in recurrent and progressive glioblastoma multiforme. J. Clin. Oncol.20, 1383–1388 (2002).
  • Bramhall SR, Schulz J, Nemunaitis J et al. A double-blind placebo-controlled, randomized study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br. J. Cancer87, 161–167 (2002).
  • King J, Zhao J, Clingan P, Morris D. Randomised double-blind placebo control study of adjuvant treatment with the metalloproteinase inhibitor marimastat in patients with inoperable colorectal hepatic metastases: significant survival advantage in patients with musculoskeletal side effects. Anticancer Res.23, 639–645 (2003).
  • Uria JA, Lopez-Otin C. Matrilysin-2, a new matrix metalloproteinase expressed in human tumors and showing the minimal domain organization required for secretion, latency, and activity. Cancer Res.60, 4745–4751 (2000).
  • Pahl HL. Activators and target genes of Rel/NFκB transcription factors. Oncogene18, 6853–6866 (1999).
  • Shaulian E, Karin M. AP-1 in cell proliferation and survival. Oncogene20, 2390–2400 (2001).
  • Kondraganti S, Mohanam S, Chintala SK et al. Selective suppression of matrix metalloproteinase-9 in human glioblastoma cells by antisense gene transfer impairs glioblastoma cell invasion. Cancer Res.60, 6851–6855 (2000).
  • Nagavarapu U, Relloma K, Herron GS. Membrane Type 1 matrix metalloproteinase regulates cellular invasiveness and survival in cutaneous epidermal cells. J. Invest. Dermatol.118, 573–581 (2002).
  • Ala-Aho R, Grenman R, Seth P, Kähäri VM. Adenoviral delivery of p53 gene suppresses expression of collagenase-3 (MMP-13) in squamous cells. Oncogene21, 1187–1195 (2000).
  • Ma Z, Qin H, Benveniste EN. Transcriptional suppression of matrix metalloproteinase-9 expression by IFN-γ and IFN-α: critical role of STAT-1α. J. Immunol.167, 5150–5159 (2001).
  • Slaton JW, Karashima T, Perrotte P et al. Treatment with low-dose interferon-α restores the balance between matrix metalloproteinase-9 and E-cadherin expression in human transitional cell carcinoma of the bladder. Clin. Cancer Res.7, 2840–2853 (2001).
  • Mengshol JA, Mix KS, Brinckerhoff CE. Matrix metalloproteinases as therapeutic targets in arthritic diseases: bull’s-eye or missing the mark? Arthritis Rheum.46, 13–20 (2002).
  • Lal A, Glazer CA, Martinson HM et al. Mutant epidermal growth factor receptor upregulates molecular effectors of tumor invasion. Cancer Res.62, 3335–3339 (2002).
  • Overall CM, Wrana JL, Sodeck J. Independent regulation of collagenase 72 kDa-progelatinase and metalloproteinase inhibitor expression in human fibroblasts by transforming growth factor α. J. Biol. Chem.264, 1860–1869 (1989).
  • Uria JA, Jimenez MG, Balbin M, Freije JMP, Lopez-Otin C. Differential effects of transforming growth factor α on the expression of collagenase-1 and collagenase-3 in human fibroblasts. J. Biol. Chem.273, 9769–9777 (1998).
  • Muraoka RS, Dumont N, Ritter CA et al. Blockade of TGF-α inhibits mammary tumor cell viability, migration and metastases. J. Clin. Invest.109, 1551–1559 (2002).
  • McGaha TL, Phelps RG, Spiera H, Bona C. Halofuginone, an inhibitor of type-I collagen synthesis and skin sclerosis, blocks transforming growth factor-α-mediated Smad3 activation in fibroblasts. J. Invest. Dermatol.118, 461–470 (2002).
  • Shin M, Yan C, Boyd D. An inhibitor of c-jun aminoterminal kinase (SP600125) represses c-jun activation, DNA-binding and PMA-inducible 92 kDa Type IV collagenase expression. Biochim. Biophys. Acta1589, 311–316 (2002).
  • Futamura M, Kamiya S, Tsukamoto M et al. Malolactomycin D, a potent inhibitor of transcription controlled by the Ras responsive element, inhibits Ras-mediated transformation activity with suppression of MMP-1 and MMP-9 in NIH3T3 cells. Oncogene20, 6724–6730 (2001).
  • Zhang Y, Thant AA, Machida K et al. Hyaluronan-CD44s signaling regulates matrix metalloproteinase-2 secretion in a human lung carcinoma cell line QG90. Cancer Res.62, 3962–3965 (2002).
  • Sato T, Koike L, Miyta Y et al. Inhibition of activator protein-1 binding activity and phosphatidylinositol 3-kinase pathway by nobiletin, a polymethoxy flavonoid, results in augmentation of tissue inhibitor of metalloproteinase-1 production and suppression of production of matrix metalloproteinase-1 and -9 in human fibrosarcoma HT-1080 cells. Cancer Res.62, 1025–1029 (2002).
  • Messina MJ, Persky V, Setchell KD, Barnes S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr. Cancer21, 113–131 (1994).
  • Fotis T, Pepper M, Adlercreutz H et al. Genistein, a dietary ingestional isoflavonoid, inhibits cell proliferation and in vivo angiogenesis. J. Nutr.125, 790–797 (1995).
  • Myoung H, Hong SP, Yun PY, Lee JU, Kim MJ. Anticancer effect of genistein in oral squamous cell carcinoma with respect to angiogenesis and in vitro invasion. Cancer Sci.94, 215–220 (2003).
  • Mukhtar H, Ahmad N. Tea polyphenols: prevention of cancer and optimizing health. Am. J. Clin. Nutr.71, 1698S–1702S (2000).
  • Oku N, Matsukawa M, Yamakawa et al. Inhibitory effect of green tea polyphenols on membrane-type 1 matrix metalloproteinase, MT1-MMP. Biol. Pharm. Bull.26, 1235–1238 (2003).
  • Garbisa S, Sartor L, Biggin S et al. Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin-3-gallate. Cancer91, 822–832 (2001).
  • Demeule M, Brossard M, Page M et al. Matrix metalloproteinase inhibition by green tea catechins. Biochim. Biophys. Acta1478, 51–60 (2000).
  • Gupta S, Ahmad N, Nieminen AL, Mukhtar H. Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (-)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells. Toxicol. Appl. Pharmacol.164, 82–90 (2000).
  • Ahmad N, Cheng P, Mukhtar H. Cell cycle dysregulation by green tea polyphenol epigallocatechin-3-gallate. Biochim. Biophys. Res. Commun.275, 328–334 (2000).
  • Lin JK, Liang YC, Lin-Shiau SY. Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. Biochem. Pharmacol.58, 911–915 (1999).
  • Mohandas KM, Desai DC. Epidemiology of digestive tract cancers in India. Ind. J. Gastroenterol.18, 118–121 (1999).
  • Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res.23, 363–398 (2003).
  • Thaloor D, Singh AK, Sidhu GS et al. Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin. Cell Growth Differ.9, 305–312 (1998).
  • Okashi Y, Tsuchiya Y, Koizumi K, Sakurai H, Saiki I. Prevention of intrahepatic metastasis by curcumin in an orthotopic implantation model. Oncology65, 250–258 (2003).
  • Shao ZM, Shen ZZ, Liu CH et al. Curcumin exerts multiple suppressive effects on human breast carcinoma cells. Int. J. Cancer98, 234–240 (2002).
  • Santibanez JF, Quintanilla M, Martinez J. Genistein and curcumin block TGF-α 1-induced u-PA expression and migratory and invasive phenotype in mouse epidermal keratinocytes. Nutr. Cancer37, 49–54 (2000).
  • Wartenberg M, Budde P, De Marees M et al. Inhibition of tumor-induced angiogenesis and matrix metalloproteinase expression in confrontation cultures of embryoid bodies and tumor spheroids by plant ingredients used in traditional chinese medicine. Lab. Invest.83, 87–98 (2003).

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