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Lycopene in Cancer Prevention

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Abstract

Lycopene, a red-colored carotenoid, present in many fruits and vegetables, including tomatoes and their processed products, watermelon, guava, carrots, pink grapefruit, and sweet potatoes, is inversely associated with the risk of many cancers. Unlike beta-carotene, lycopene lacks a beta-ionone ring and therefore has no provitamin A activity. However, the 11 conjugated and two nonconjugated double bonds in lycopene make it highly reactive toward oxygen and free radicals. Lycopene has been proposed to protect against cancer through various properties including decreased lipid oxidation, inhibition of cancer cell proliferation, and most notably potent antioxidant properties, apoptosis, increased gap-junctional communication, interferences in insulin-like growth factor 1 receptor signaling pathways, and cell cycle progression. Preclinical studies and clinical trials show that lycopene has potent in vitro and in vivo antitumor effects, suggesting potential preventive and therapeutic roles for lycopene. Further mechanistic studies and randomized controlled clinical intervention trials with lycopene in cancer patients are warranted. In this chapter, cancer prevention using lycopene is reviewed and the possible mechanisms of action are described.

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Abbreviations

4-NQO:

4-nitroquinoline-1-oxide

5-LOX:

5-lipoxygenase

ABCA1:

ATP-binding cassette transporter 1

ACF:

Aberrant crypt foci

AFB1:

Aflatoxin B1

ALOX5:

Arachidonate 5-lipoxygenase

AOM:

Azoxymethane

ARE:

Antioxidant response element

BPH:

Benign prostate hypertrophy

BQE:

Betel quid extract

BRCA:

Breast cancer

CAT:

Catalase

CDK:

Cyclin-dependent kinases

CI:

Confidence interval

COX-2:

Cyclooxygenase-2

CSE:

Cigarette smoke extract

Cx43:

Connexin 43

DEN:

Diethylnitrosamine

DMBA:

7,12-dimethyl-benz[a]anthracene

DMH:

1,2-dimethylhydrazine

EGCG:

Epigallocatechin gallate

EPHX1:

Epoxide hydrolase 1

ER:

Estrogen receptor

FLAP:

5-LOX-activating protein

GJC:

Gap-junctional intercellular communication

GnRH:

Gonadotropin-releasing hormone

GSK-3β:

Glycogen synthase kinase-3β

HCC:

Hepatocellular carcinoma

HepG2:

Human hepatocellular liver carcinoma cell line

HFD:

High-fat diet

HGPIN:

High-grade prostatic intraepithelial neoplasia

IGF-1:

Insulin-like growth factor

IGFBP-3:

Insulin-like growth factor binding protein 3

IL:

Interleukin

Keap-1:

Kelch-like ECH-associated protein 1

LEC:

Long-Evans Cinnamon

LXRα:

Liver X receptor alpha

MCF-7:

Human breast adenocarcinoma cell line

MMP:

Matrix metalloproteinase

MNNG:

N-methyl-N′-nitro-N-nitrosoguanidine

MNU:

N-methyl-N-nitrosourea

NASH:

Nonalcoholic steatohepatitis

NF-kB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NHANES:

National Health and Nutrition Examination Survey

NNK:

4-(N-methyl-N-nitrosamino)-1-(3-pyridal)-1-butanone

Nrf2:

Nuclear factor-E2-related factor 2

NSAIDs:

Nonsteroidal anti-inflammatory drugs

ORs:

Odds ratios

PanIN:

Pancreatic intraepithelial neoplasias

PCB:

Polychlorinated biphenyls

PCNA:

Proliferating cellular nuclear antigen

PGIS:

Prostacyclin synthase

PGST:

Placental glutathione-S-transferase

PPAR:

Peroxisome proliferator-activated receptor

PPARγ:

Peroxisome proliferator-activated receptor gamma

PSA:

Prostate-specific antigen

RAR:

Retinoic acid receptor

RCC:

Renal cell carcinoma

RR:

Relative risk

SOD:

Superoxide dismutase

TE:

Tomato extract

TF:

The metal-binding protein transferrin

THP1:

Human acute monocytic leukemia cell line

TNF-α:

Tumor necrosis factor-alpha

References

  1. U.S. National Research Council (1989) Diet and health: implications for reducing chronic disease risk. The National Academies Press, Washington, DC

    Google Scholar 

  2. American Cancer Society (1984) Nutrition and cancer: causation and prevention. An American Cancer Society special report. CA Cancer J Clin 34:5–10

    Google Scholar 

  3. Lee BM, Park KK (2003) Beneficial and adverse effects of chemopreventive agents. Mutat Res 523–524:265–278

    Google Scholar 

  4. Tanaka T, Shinimizu M, Moriwaki H (2012) Cancer chemoprevention by carotenoids. Molecules 17:3202–3242

    Article  CAS  Google Scholar 

  5. Giovannucci E (2002) A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Exp Biol Med 227:852–859

    CAS  Google Scholar 

  6. Omoni A, Aluko RE (2005) The anti-carcinogenic and anti-atherogenic effects of lycopene: a review. Trends Food Sci Technol 16:344–350

    Article  CAS  Google Scholar 

  7. Olson JA, Krinsky NI (1995) Introduction: the colorful, fascinating world of the carotenoids: important physiologic modulators. FASEB J 9:1547–1550

    CAS  Google Scholar 

  8. van Breemen RB, Pajkovic N (2008) Multitargeted therapy of cancer by lycopene. Cancer Lett 269:339–351

    Article  CAS  Google Scholar 

  9. Lu R, Dan H, Wu R, Meng W, Liu N, Jin X, Zhou M, Zeng X, Zhou G, Chen Q (2011) Lycopene: features and potential significance in the oral cancer and precancerous lesions. J Oral Pathol Med 40:361–368

    Article  CAS  Google Scholar 

  10. Uppala PT, Dissmore T, Lau BH, Andacht T, Rajaram S (2012) Selective inhibition of cell proliferation by lycopene in MCF–7 breast cancer cells in vitro: a proteomic analysis. Phytother Res. doi:10.1002/ptr.4764

    Google Scholar 

  11. Al-Malki AL, Moselhy SS, Refai MY (2012) Synergistic effect of lycopene and tocopherol against oxidative stress and mammary tumorigenesis induced by 7,12-dimethyl[a]benzanthracene in female rats. Toxicol Ind Health 28:542–548

    Article  CAS  Google Scholar 

  12. Sahin K, Tuzcu M, Sahin N, Akdemir F, Ozercan I, Bayraktar S, Kucuk O (2011) Inhibitory effects of combination of lycopene and genistein on 7,12-dimethyl benz(a)anthracene-induced breast cancer in rats. Nutr Cancer 63:1279–1286

    Article  CAS  Google Scholar 

  13. Yang CM, Hu TY, Hu ML (2012) Antimetastatic effects and mechanisms of apo-8′-lycopenal, an enzymatic metabolite of lycopene, against human hepatocarcinoma SK-Hep-1 cells. Nutr Cancer 64:274–285

    Article  CAS  Google Scholar 

  14. Yang CM, Lu IH, Chen HY, Hu ML (2012) Lycopene inhibits the proliferation of androgen-dependent human prostate tumor cells through activation of PPARγ-LXRα-ABCA1 pathway. J Nutr Biochem 23:8–17

    Article  CAS  Google Scholar 

  15. Yang CM, Lu YL, Chen HY, Hu ML (2011) Lycopene and the LXRα agonist T0901317 synergistically inhibit the proliferation of androgen-independent prostate cancer cells via the PPARγ-LXRα-ABCA1 pathway. J Nutr Biochem 23:1155–1162

    Article  CAS  Google Scholar 

  16. Ford NA, Elsen AC, Zuniga K, Lindshield BL, Erdman JW Jr (2011) Lycopene and apo-12′-lycopenal reduce cell proliferation and alter cell cycle progression in human prostate cancer cells. Nutr Cancer 63:256–263

    Article  CAS  Google Scholar 

  17. Lin MC, Wang FY, Kuo YH, Tang FY (2011) Cancer chemopreventive effects of lycopene: suppression of MMP–7 expression and cell invasion in human colon cancer cells. J Agric Food Chem 59:11304–11318

    Article  CAS  Google Scholar 

  18. Luo C, Wu XG (2011) Lycopene enhances antioxidant enzyme activities and immunity function in N-methyl-N′-nitro-N-nitrosoguanidine-induced gastric cancer rats. Int J Mol Sci 12:3340–3351

    Article  CAS  Google Scholar 

  19. Ettorre A, Frosali S, Andreassi M, Di Stefano A (2010) Lycopene phytocomplex, but not pure lycopene, is able to trigger apoptosis and improve the efficacy of photodynamic therapy in HL60 human leukemia cells. Exp Biol Med (Maywood) 235:1114–1125

    Article  CAS  Google Scholar 

  20. Palozza P, Colangelo M, Simone R, Catalano A, Boninsegna A, Lanza P, Monego G, Ranelletti FO (2010) Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras signaling in cancer cell lines. Carcinogenesis 31:1813–1821

    Article  CAS  Google Scholar 

  21. Salman H, Bergman M, Djaldetti M, Bessler H (2007) Lycopene affects proliferation and apoptosis of four malignant cell lines. Biomed Pharmacother 61:366–369

    Article  CAS  Google Scholar 

  22. Levy J, Bosin E, Feldman B, Giat Y, Miinster A, Danilenko M, Sharoni Y (1995) Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta-carotene. Nutr Cancer 24:257–266

    Article  CAS  Google Scholar 

  23. Bertram JS (1999) Carotenoids and gene regulation. Nutr Rev 57:182–191

    Article  CAS  Google Scholar 

  24. Amir H, Karas M, Giat J, Danilenko M, Levy R, Yermiahu T, Levy J, Sharoni Y (1999) Lycopene and 1,25-dihydroxyvitamin D3 cooperate in the inhibition of cell cycle progression and induction of differentiation in HL–60 leukemic cells. Nutr Cancer 33:105–112

    Article  CAS  Google Scholar 

  25. Park CK, Ishimi Y, Ohmura M, Yamaguchi M, Ikegami S (1997) Vitamin A and carotenoids stimulate differentiation of mouse osteoblastic cells. J Nutr Sci Vitaminol 43:281–296

    Article  CAS  Google Scholar 

  26. Karas M, Amir H, Fishman D, Danilenko M, Segal S, Nahum A, Koifmann A, Giat Y, Levy J, Sharoni Y (2000) Lycopene interferes with cell cycle progression and insulin-like growth factor I signaling in mammary cancer cells. Nutr Cancer 36:101–111

    Article  CAS  Google Scholar 

  27. Rajah R, Valentinis B, Cohen P (1997) Insulin-like growth factor (IGF)-binding protein–3 induces apoptosis and mediates the effects of transforming growth factor-beta–1 on programmed cell death through a p53- and IGF-independent mechanism. J Biol Chem 272:12181–12188

    Article  CAS  Google Scholar 

  28. Chan JM, Stampfer MJ, Giovanucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M (1998) Plasma insulin-like growth factor–1 and prostate cancer risk: a prospective study. Science 279:563–566

    Article  CAS  Google Scholar 

  29. Giovannucci E (1999) Insulin-like growth factor-I and binding protein–3 and risk of cancer. Horm Res 51:34–41

    Article  CAS  Google Scholar 

  30. Mehta PP, Bertram JS, Loewenstein WR (1989) The actions of retinoids on cellular growth correlate with their actions on gap junctional communication. Cell Biol 108:1053–1065

    Article  CAS  Google Scholar 

  31. Hossain MZ, Wilkens LR, Mehta PP, Loewenstein W, Bertram JS (1989) Enhancement of gap junctional communication by retinoids correlates with their ability to inhibit neoplastic transformation. Carcinogenesis 10:1743–1748

    Article  CAS  Google Scholar 

  32. Zhang LX, Cooney RV, Bertram JS (1992) Carotenoids up-regulate connexin43 gene expression independent of their pro-vitamin A or antioxidant properties. Cancer Res 52:5707–5712

    CAS  Google Scholar 

  33. Wertz K, Siler U, Goralczyk R (2004) Lycopene: modes of action to promote prostate health. Arch Biochem Biophys 430:127–134

    Article  CAS  Google Scholar 

  34. Bertram JS, Pung A, Churley M, Kappock TJ 4th, Wilkins LR, Cooney RV (1991) Diverse carotenoids protect against chemically induced neoplastic transformation. Carcinogenesis 12:671–678

    Article  CAS  Google Scholar 

  35. Gius D, Botero A, Shah S, Curry HA (1999) Intracellular oxidation/reduction status in the regulation of transcription factors NF-kappaB and AP–1. Toxicol Lett 106:93–106

    Article  CAS  Google Scholar 

  36. Riso P, Pinder A, Santangelo A, Porrini M (1999) Does tomato consumption effectively increase the resistance of lymphocyte DNA to oxidative damage? Am J Clin Nutr 69:712–718

    CAS  Google Scholar 

  37. Rao AV, Fleshner N, Agarwal S (1999) Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study. Nutr Cancer 33:159–164

    Article  CAS  Google Scholar 

  38. Siler U, Barella L, Spitzer V, Scnorr J, Lein M, Goralczyk R, Wertz K (2004) Lycopene and vitamin E interfere with autocrine/paracrine loops in the Dunning prostate cancer model. FASEB J 18:1019–1021

    CAS  Google Scholar 

  39. Hazai E, Bikadi Z, Zsila S, Lockwood SF (2006) Molecular modeling of the non-covalent binding of the dietary tomato carotenoids lycopene and lycophyl, and selected oxidative metabolites with 5-lipoxygenase. Bioorg Med Chem 14:6859–6867

    Article  CAS  Google Scholar 

  40. Jewell C, O'Brien NM (1999) Effect of dietary supplementation with carotenoids on xenobiotic metabolizing enzymes in the liver, lung, kidney and small intestine of the rat. Br J Nutr 81:235–242

    CAS  Google Scholar 

  41. Chew BP, Park JS (2004) Carotenoid action on the immune response. J Nutr 134:257–261

    Google Scholar 

  42. Heber D, Lu QY (2002) Overview of mechanisms of action of lycopene. Exp Biol Med (Maywood) 227:920–923

    CAS  Google Scholar 

  43. Goralczyk R, Siler U (2003) The role of lycopene in health and disease. In: Fenwick R (ed) Phytochemicals in health and disease. Dekker, New York, pp 285–309

    Google Scholar 

  44. Ben-Dor A, Steiner M, Gheber L, Danilenko M, Dubi N, Linnewiel K, Zick A, Sharoni Y, Levy J (2005) Carotenoids activate the antioxidant response element transcription system. Mol Cancer Ther 4:177–186

    CAS  Google Scholar 

  45. Goo YA, Li Z, Pajkovic N, Shaffer S, Taylor G, Chen J, Campbell D, Arnstein L, Goodlett DR, van Breemen RB (2007) Systematic investigation of lycopene effects in LNCaP cells by use of novel large-scale proteomic analysis software. Proteomics Clin Appl 1:513–523

    Article  CAS  Google Scholar 

  46. Seren S, Lieberman R, Bayraktar UD, Heath E, Sahin K, Andic F, Kucuk O (2008) Lycopene in cancer prevention and treatment. Am J Ther 15:66–68

    Article  Google Scholar 

  47. Neveu M, Bertram JS (2000) Gap junctions and neoplasia. In: Hetzberg EL, Bittar EE (eds) Gap junctions. JAI Press, Greenwich, pp 221–262

    Chapter  Google Scholar 

  48. Lee SW, Tomasetto C, Sager R (1991) Positive selection of candidate tumor suppressor genes by subtractive hybridization. Proc Natl Acad Sci USA 88:2825–2829

    Article  CAS  Google Scholar 

  49. Omori Y, Yamasaki H (1998) Mutated connexin43 proteins inhibit rat glioma cell growth suppression mediated by wild-type connexin43 in a dominant- negative manner. Int J Cancer 78:446–453

    Article  CAS  Google Scholar 

  50. Hossain MZ, Bertram JS (1994) Retinoids suppress proliferation, induce cell spreading, and up-regulate connexin43 expression only in postconfluent 10 T1/2 cells: implications for the role of gap junctional communication. Cell Growth Diff 5:1253–1261

    CAS  Google Scholar 

  51. King TJ, Fukushima LH, Hieber AD, Shimabukuro KA, Sakr WA, Bertram JS (2000) Reduced levels of connexin 43 in cervical dysplasia: inducible expression in a cervical carcinoma cell line decreases neoplastic potential with implications for tumor progression. Carcinogenesis 21:1097–1109

    Article  CAS  Google Scholar 

  52. Loewenstein WR (1979) Junctional intercellular communication and the control of growth. Biochem Biophys Acta 560:1–65

    CAS  Google Scholar 

  53. Tsai H, Werber J, Davia MO, Edelman M, Tanaka KE, Melman A, Christ GJ, Geliebter J (1996) Reduced connexin 43 expression in high grade, human prostatic adenocarcinoma cells. Biochem Biophys Res Commun 22:64–69

    Article  Google Scholar 

  54. Hossain MZ, Jagdale AB, Ao P, LeCiel C, Huang RP, Boynton AL (1999) Impaired expression and posttranslational processing of connexin 43 and downregulation of gap junctional communication in neoplastic human prostate cells. Prostate 38:55–59

    Article  CAS  Google Scholar 

  55. Mehta P, Perez-Stable C, Nadji M, Mian M, Asotra K, Roos BA (1999) Suppression of human prostate cancer cell growth by forced expression of connexin genes. Dev Genet 24:91–110

    Article  CAS  Google Scholar 

  56. Mehta PP, Lokeshwar BL, Schiller PC, Bendix MV, Ostenson RC, Howard GA, Roos BA (1996) Gap-junctional communication in normal and neoplastic prostate epithelial cells and its regulation by cAMP. Mol Carcinog 15:18–32

    Article  CAS  Google Scholar 

  57. Walfisch S, Walfisch Y, Kirilov E, Linde N, Mnitentag H, Agbaria R, Sharoni Y, Levy J (2007) Tomato lycopene extract supplementation decreases insulin-like growth factor-I levels in colon cancer patients. Eur J Cancer Prev 16:298–303

    Article  CAS  Google Scholar 

  58. Cohen P, Peehl DM, Rosenfeld RG (1994) The IGF axis in the prostate. Hormone Metab Res 26:81–84

    Article  CAS  Google Scholar 

  59. Cohen P, Peehl DM, Lamson G, Rosenfeld RG (1991) Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial cells. J Clin Endocrinol Metab 73:401–407

    Article  CAS  Google Scholar 

  60. Tang FY, Shih CJ, Cheng LH, Ho HJ, Chen HJ (2008) Lycopene inhibits growth of human colon cancer cells via suppression of the Akt signaling pathway. Mol Nutr Food Res 52:646–654

    Article  CAS  Google Scholar 

  61. Ghosh J, Myers CE (2002) Molecular mechanisms of prostate cancer cell death triggered by inhibition of arachidonate 5-lipoxygenase: involvement of Fas death receptor-mediated signals. Adv Exp Med Biol 507:415–420

    Article  CAS  Google Scholar 

  62. Simone RE, Russo M, Catalano A, Monego G, Froehlich K, Boehm V, Palozza P (2011) Lycopene inhibits NF-kB-mediated IL–8 expression and changes redox and PPARgamma signalling in cigarette smoke-stimulated macrophages. PLoS One 6:e19652

    Article  CAS  Google Scholar 

  63. Klarod K, Hongsprabhas P, Khampitak T, Wirasorn K, Kiertiburanakul S, Tangrassameeprasert R, Daduang J, Yongvanit P, Boonsiri P (2011) Serum antioxidant levels and nutritional status in early and advanced stage lung cancer patients. Nutrition 27:1156–1160

    Article  CAS  Google Scholar 

  64. Graham DL, Carail M, Caris-Veyrat C, Lowe GM (2010) Cigarette smoke and human plasma lycopene depletion. Food Chem Toxicol 48:2413–2420

    Article  CAS  Google Scholar 

  65. Choi SH, Lee SH, Kim HJ, Lee IS, Kozukue N, Levin CE, Friedman M (2010) Changes in free amino acid, phenolic, chlorophyll, carotenoid, and glycoalkaloid contents in tomatoes during 11 stages of growth and inhibition of cervical and lung human cancer cells by green tomato extracts. Agric Food Chem 58:7547–7556

    Article  CAS  Google Scholar 

  66. Michaud DS, Feskanich D, Rimm EB, Colditz GA, Speizer FE, Willett WC, Giovannucci E (2000) Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts. Am J Clin Nutr 72:990–997

    CAS  Google Scholar 

  67. Holick CN, Michaud DS, Stolzenberg-Solomon R, Mayne ST, Pietinen P, Taylor PR, Virtamo J, Albanes D (2002) Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the alpha-tocopherol, beta-carotene cohort study. Am J Epidemiol 156:536–547

    Article  Google Scholar 

  68. Knekt P, Järvinen R, Teppo L, Aromaa A, Seppänen R (1999) Role of various carotenoids in lung cancer prevention. J Natl Cancer Inst 91:182–184

    Article  CAS  Google Scholar 

  69. Comstock GW, Helzlsouer KJ, Bush TL (1991) Prediagnostic serum levels of carotenoids and vitamin E as related to subsequent cancer in Washington County, Maryland. Am J Clin Nutr 53:260–264

    Google Scholar 

  70. Axelsson G, Liljeqvist T, Andersson L, Bergman B, Rylander R (1996) Dietary factors and lung cancer among men in west Sweden. Int J Epidemiol 25:32–39

    Article  CAS  Google Scholar 

  71. Bond GG, Thompson FE, Cook RR (1987) Dietary vitamin A and lung cancer: results of a case–control study among chemical workers. Nutr Cancer 9:109–121

    Article  CAS  Google Scholar 

  72. De Stefani E, Boffetta P, Deneo-Pellegrini H, Mendilaharsu M, Carzoglio JC, Ronco A, Olivera L (1999) Dietary antioxidants and lung cancer risk: a case-control study in Uruguay. Nutr Cancer 34:100–110

    Article  CAS  Google Scholar 

  73. Brennan P, Fortes C, Butler J, Agudo A, Benhamou S, Darby S, Gerken M, Jökel KH, Kreuzer M, Mallone S, Nyberg F, Pohlabeln H, Ferro G, Boffetta P (2000) A multi-center case control study of diet and lung cancer among non-smokers. Cancer Causes Control 11:49–58

    Article  CAS  Google Scholar 

  74. Goodman MT, Kolonel LN, Wilkens LR, Yoshizawa CN, Le Marchand L, Hankin JH (1992) Dietary factors in lung cancer prognosis. Eur J Cancer 28:495–501

    Article  CAS  Google Scholar 

  75. Garcia-Closas R, Agudo A, Gonzalez CA, Riboli E (1998) Intake of specific carotenoids and flavonoids and the risk of lung cancer in women in Barcelona, Spain. Nutr Cancer 32:154–158

    Article  CAS  Google Scholar 

  76. Ito Y, Wakai K, Suzuki K, Tamakoshi A, Seki N, Ando M, Nishino Y, Kondo T, Watanabe Y, Ozasa K, Ohno Y, JACC Study Group (2003) Serum carotenoids and mortality from lung cancer: a case–control study nested in the Japan Collaborative Cohort (JACC) study. Cancer Sci 94:57–63

    Article  CAS  Google Scholar 

  77. Muscat JE, Huncharek M (1996) Dietary intake and the risk of malignant mesothelioma. Br J Cancer 73:1122–1125

    Article  CAS  Google Scholar 

  78. Lian F, Smith DE, Ernst H, Russell RM, Wang XD (2007) Apo–10′–lycopenoic acid inhibits lung cancer cell growth in vitro, and suppresses lung tumorigenesis in the A/J mouse model in vivo. Carcinogenesis 28:1567–1574

    Article  CAS  Google Scholar 

  79. Lian F, Wang XD (2008) Enzymatic metabolites of lycopene induce Nrf2–mediated expression of phase II detoxifying/antioxidant enzymes in human bronchial epithelial cells. Int J Cancer 123:1262–1268

    Article  CAS  Google Scholar 

  80. Kim DJ, Takasuka N, Nishino H, Tsuda H (2000) Chemopreventiopn of lung cancer by lycopene. Biofactors 13:95–102

    Article  CAS  Google Scholar 

  81. Liu C, Lian F, Smith DE, Russell RM, Wang XD (2003) Lycopene supplementation inhibits lung squamous metaplasia and induces apoptosis via up-regulating insulin-like growth factor-binding protein 3 in cigarette smoke-exposed ferrets. Cancer Res 63:3138–3144

    CAS  Google Scholar 

  82. Liu C, Russell RM (2008) Nutrition and gastric cancer risk: an update. Nutr Rev 66:237–249

    Article  Google Scholar 

  83. Lunet N, Lacerda-Vieira A, Barros H (2005) Fruit and vegetables consumption and gastric cancer: a systematic review and meta-analysis of cohort studies. Nutr Cancer 53:1–10

    Article  Google Scholar 

  84. Fan XM, Tu SP, Lam SK, Wang WP, Wu J, Wong WM, Yuen MF, Lin MC, Kung HF, Wong BC (2004) Five-lipoxygenase-activating protein inhibitor MK–886 induces apoptosis in gastric cancer through upregulation of p27kip1 and bax. J Gastroenterol Hepatol 19:31–37

    Article  CAS  Google Scholar 

  85. Botterweck AA, van den Brandt PA, Goldbohm RA (2000) Vitamins, carotenoids, dietary fiber, and the risk of gastric carcinoma: results from a prospective study after 6.3 years of follow-up. Cancer 88:737–748

    Article  CAS  Google Scholar 

  86. Haenszel W, Kurihara M, Segi M, Lee RK (1972) Stomach cancer among Japanese in Hawaii. J Natl Cancer Inst 49:969–988

    CAS  Google Scholar 

  87. Modan B, Cuckle H, Lubin F (1981) A note on the role of dietary retinol and carotene in human gastro-intestinal cancer. Int J Cancer 28:421–424

    Article  CAS  Google Scholar 

  88. Franceschi S, Bidoli E, La Vecchia C, Talamini R, D'Avanzo B, Negri E (1994) Tomatoes and risk of digestive-tract cancers. Int J Cancer 59:181–184

    Article  CAS  Google Scholar 

  89. Buiatti E, Palli D, Decarli A, Amadori D, Avellini C, Bianchi S, Biserni R, Cipriani F, Cocco P, Giacosa A, Marubini E, Puntoni R, Vindigni C, Fraumeni J Jr, Blot W (1989) A case-control study of gastric cancer and diet in Italy. Int J Cancer 44:611–616

    Article  CAS  Google Scholar 

  90. Boeing H, Jedrychowski W, Wahrendorf J, Popiela T, Tobiasz-Adamczyk B, Kulig A (1991) Dietary risk factors in intestinal and diffuse types of stomach cancer: a multicenter case–control study in Poland. Cancer Causes Control 2:227–233

    Article  CAS  Google Scholar 

  91. Hansson LE, Nyrén O, Bergström R, Wolk A, Lindgren A, Baron J, Adami HO (1993) Diet and risk of gastric cancer. A population–based case–control study in Sweden. Int J Cancer 55:181–189

    Article  CAS  Google Scholar 

  92. Yuan JM, Ross RK, Gao YT, Qu YH, Chu XD, Yu MC (2004) Prediagnostic levels of serum micronutrients in relation to risk of gastric cancer in Shangai, China. Cancer Epidemiol Biomarkers Prev 13:1772–1780

    CAS  Google Scholar 

  93. Pelucchi C, Tramacere I, Bertuccio P, Tavani A, Negri E, La Vecchia C (2009) Dietary intake of selected micronutrients and gastric cancer risk: an Italian case–control study. Ann Oncol 20:160–165

    Article  CAS  Google Scholar 

  94. Velmurugan B, Mani A, Nagini S (2005) Combination of S–allylcysteine and lycopene induces apoptosis by modulating Bcl–2, Bax, Bim and caspases during experimental gastric carcinogenesis. Eur J Cancer Prev 14:387–393

    Article  CAS  Google Scholar 

  95. Velmurugan B, Bhuvaneswari V, Nagini S (2002) Antiperoxidative effects of lycopene during N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis. Fitoterapia 73:604–611

    Article  CAS  Google Scholar 

  96. Velmurugan B, Bhuvaneswari V, Burra UK, Nagini S (2002) Prevention of N-methyl-N′nitro-N-nitrosoguanidine and saturated sodium chloride-induced gastric carcinogenesis in Wistar rats by lycopene. Eur J Cancer Prev 11:19–26

    Article  CAS  Google Scholar 

  97. Liu C, Russell RM, Wang XD (2006) Lycopene supplementation prevents smoke–induced changes in p53, p53 phosphorylation, cell proliferation, and apoptosis in the gastric mucosa of ferrets. J Nutr 136:106–111

    CAS  Google Scholar 

  98. Persson C, Sasazuki S, Inoue M, Kurahashi N, Iwasaki M, Miura T, Ye W, Tsugane S, JPHC Study Group (2008) Plasma levels of carotenoids, retinol and tocopherol and the risk of gastric cancer in Japan: a nested case control study. Carcinogenesis 29:1042–1048

    Article  CAS  Google Scholar 

  99. Steinmetz KA, Potter JD (1996) Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc 96:1027–1039

    Article  CAS  Google Scholar 

  100. Hu F, Wang Yi B, Zhang W, Liang J, Lin C, Li D, Wang F, Pang D, Zhao Y (2012) Carotenoids and breast cancer risk: a meta-analysis and meta-regression. Breast Cancer Res Treat 131:239–253

    Article  CAS  Google Scholar 

  101. Sesso HD, Buring JE, Zhang SM, Norkus EP, Gaziano JM (2005) Dietary and plasma lycopene and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 14:1074–1081

    Article  CAS  Google Scholar 

  102. Terry P, Jain M, Miller AB, Howe GR, Rohan TE (2002) Dietary carotenoids and risk of breast cancer. Am J Clin Nutr 76:883–888

    CAS  Google Scholar 

  103. Sato R, Helzlsouer KJ, Alberg AJ, Hoffman SC, Norkus EP, Comstock GW (2002) Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 11:451–457

    CAS  Google Scholar 

  104. Zhang S, Tang G, Russell RM, Mayzel KA, Stampfer MJ, Willett WC, Hunter DJ (1997) Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects. Am J Clin Nutr 66:626–632

    CAS  Google Scholar 

  105. Dorjgochoo T, Gao YT, Chow WH, Shu XO, Li H, Yang G, Cai Q, Rothman N, Cai H, Franke AA, Zheng W, Dai Q (2009) Plasma carotenoids, tocopherols, retinol and breast cancer risk: results from the Shanghai Women Health Study (SWHS). Breast Cancer Res Treat 117:381–389

    Article  CAS  Google Scholar 

  106. Wang H, Leung LK (2010) The carotenoid lycopene differentially regulates phase I and II enzymes in dimethylbenz[a]anthracene-induced MCF–7 cells. Nutrition 26:1181–1187

    Article  CAS  Google Scholar 

  107. Sharoni Y, Giron E, Rise M, Levy J (1997) Effects of lycopene-enriched tomato oleoresin on 7,12-dimethyl-benz[a]anthracene-induced rat mammary tumors. Cancer Detect Prev 21:118–123

    CAS  Google Scholar 

  108. Moselhy SS, Al Mslmani MA (2008) Chemopreventive effect of lycopene alone or with melatonin against the genesis of oxidative stress and mammary tumors induced by 7,12 dimethyl(a)benzanthracene in sprague dawely female rats. Mol Cell Biochem 319:175–180

    Article  CAS  Google Scholar 

  109. Cohen LA, Zhao Z, Pittman B, Khachik F (1999) Effect of dietary lycopene on N-methylnitrosourea- induced mammary tumorigenesis. Nutr Cancer 34:153–159

    Article  CAS  Google Scholar 

  110. Chalabi N, Le Corre L, Maurizis JC, Bignon YJ, Bernard-Gallon DJ (2004) The effects of lycopene on the proliferation of human breast cells and BRCA1 and BRCA2 gene expression. Eur J Cancer 40:1768–1775

    Article  CAS  Google Scholar 

  111. Li Z, Wang Y, Mo B (2002) The effects of carotenoids on the proliferation of human breast cancer cell and gene expression of bcl–2 [Chinese]. Zhonghua Yu Fang Yi Xue Za Zhi 36:254–257

    CAS  Google Scholar 

  112. Nahum A, Hirsch K, Danilenko M, Watts CK, Prall OW, Levy J, Sharoni Y (2001) Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27 (Kip1) in the cyclin E-cdk2 complexes. Oncogene 20:3428–3436

    Article  CAS  Google Scholar 

  113. American Cancer Society (2008) Cancer prevention & early detection facts & figures 2008. American Cancer Society, Atlanta

    Google Scholar 

  114. Ganne-Carrie N, Trinchet JC (2004) Systemic treatment of hepatocellular carcinoma. Eur J Gastroenterol Hepatol 16:275–281

    Article  CAS  Google Scholar 

  115. Glauert HP, Calfee-Mason K, Stemm DN, Tharappel JC, Spear BT (2010) Dietary antioxidants in the prevention of hepatocarcinogenesis: a review. Mol Nutr Food Res 54:875–896

    Article  CAS  Google Scholar 

  116. Bosch FX, Ribes J, Diaz M, Cleries R (2004) Primary liver cancer: worldwide incidence and trends. Gastroenterology 127:5–16

    Article  Google Scholar 

  117. Seren S, Mutchnick M, Hutchinson D, Harmanci O, Bayraktar Y, Mutchnick S, Sahin K, Kucuk O (2008) Potential role of lycopene in the treatment of hepatitis C and prevention of hepatocellular carcinoma. Nutr Cancer 60:729–735

    Article  CAS  Google Scholar 

  118. Hwang ES, Lee HJ (2006) Inhibitory effects of lycopene on the adhesion, invasion, and migration of SK-Hep1 human hepatoma cells. Exp Biol Med (Maywood) 231:322–327

    CAS  Google Scholar 

  119. Huang CS, Liao JW, Hu ML (2008) Lycopene inhibits experimental metastasis of human hepatoma SK-Hep–1 cells in athymic nude mice. J Nutr 138:538–543

    Google Scholar 

  120. Burgess LC, Rice E, Fischer T, Seekins JR, Burgess TP, Sticka SJ, Klatt K (2008) Lycopene has limited effect on cell proliferation in only two of seven human cell lines (both cancerous and noncancerous) in an in vitro system with doses across the physiological range. Toxicol In Vitro 22:1297–1300

    Article  CAS  Google Scholar 

  121. Tharappel JC, Lehmler HJ, Srinivasan C, Robertson LW, Spear BT, Glauert HP (2008) Effect of antioxidant phytochemicals on the hepatic tumor promoting activity of 3,30,4,40-tetrachlorobiphenyl (PCB–77). Food Chem Toxicol 46:3467–3474

    Article  CAS  Google Scholar 

  122. Nishino H (1997) Cancer prevention by natural carotenoids. J Cell Biochem Supp 27:86–91

    Article  CAS  Google Scholar 

  123. Yu M, Chiang Y, Lien J, Chen C (1997) Plasma antioxidant vitamins, chronic hepatitis B virus infection and urinary aflatoxin B1-DNA adducts in healthy males. Carcinogenesis 18:1189–1194

    Article  CAS  Google Scholar 

  124. Gradlet S, LeBon AM, Bergès R, Suschetet M, Astorg P (1998) Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DNA damage in the rat: role of the modulation of aflatoxin B1 metabolism. Carcinogenesis 19:403–411

    Article  Google Scholar 

  125. Astorg P, Gradelet S, Berger R, Suschetet M (1997) Dietary lycopene decreases the initiation of liver preneoplastic foci by diethylnitrosamine in the rat. Nutr Cancer 29:60–68

    Article  CAS  Google Scholar 

  126. Reddy L, Odhav B, Bhoola K (2006) Aflatoxin B1-induced toxicity in HepG2 cells I nhibited by carotenoids: morphology, apoptosis and DNA damage. Biol Chem 387:87–93

    Article  CAS  Google Scholar 

  127. Watanabe S, Kitade Y, Masaki T, Nishioka M, Satoh K, Nishino H (2001) Effects of lycopene and Sho-saiko-to on hepatocarcinogenesis in a rat model of spontaneous liver cancer. Nutr Cancer 39:96–101

    Article  CAS  Google Scholar 

  128. Park YO, Hwang ES, Moon TW (2005) The effect of lycopene on cell growth and oxidative DNA damage of Hep3B human hepatoma cells. Biofactors 23:129–139

    Article  CAS  Google Scholar 

  129. Takahashi Y, Hara Y, Imanaka M, Wanibuchi H, Tanaka K, Ishikawa T, Mori S, Fukusato T (2010) No inhibitory effects of (−)-epigallocatechin gallate and lycopene on spontaneous hepatotumorigenesis in C3H/HeN mice. Fukushima J Med Sci 56:17–27

    Article  CAS  Google Scholar 

  130. Wang Y, Ausman LM, Greenberg AS, Russell RM, Wang XD (2010) Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis-promoted hepatocarcinogenesis in rats. Int J Cancer 126:1788–1796

    CAS  Google Scholar 

  131. Nitsche C, Simon P, Weiss FU, Fluhr G, Weber E, Gärtner S, Behn CO, Kraft M, Ringel J, Aghdassi A, Mayerle J, Lerch MM (2011) Environmental risk factors for chronic pancreatitis and pancreatic cancer. Dig Dis 29:235–242

    Article  Google Scholar 

  132. Nkondjock A, Ghadirian P, Johnson KC, Krewski D, Canadian Cancer Registries Epidemiology Research Group (2005) Dietary intake of lycopene is associated with reduced pancreatic cancer risk. J Nutr 135:592–597

    CAS  Google Scholar 

  133. Burney PGJ, Comstock GW, Morris JS (1989) Serologic precursors of cancer: serum micronutrients and the subsequent risk of pancreatic cancer. Am J Clin Nutr 49:895–900

    CAS  Google Scholar 

  134. Seo JY, Masamune A, Shimosegawa T, Kim H (2009) Protective effect of lycopene on oxidative stress-induced cell death of pancreatic acinar cells. Ann N Y Acad Sci 1171:570–575

    Article  CAS  Google Scholar 

  135. Sung JJ, Lau JY, Goh KL, Leung WK (2005) Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol 6:871–876

    Article  Google Scholar 

  136. Lieberman DA, Prindiville S, Weiss DG, Willett W (2003) Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals. JAMA 290:2959–2967

    Article  Google Scholar 

  137. Miller PE, Lesko SM, Muscat JE, Lazarus P, Hartman TJ (2010) Dietary patterns and colorectal adenoma and cancer risk: a review of the epidemiological evidence. Nutr Cancer 62:413–424

    Article  Google Scholar 

  138. Malila N, Virtamo J, Virtanen M, Pietinen P, Albanes D, Teppo L (2002) Dietary and serum alpha-tocopherol, beta-carotene and retinol, and risk for colorectal cancer in male smokers. Eur J Clin Nutr 56:615–621

    Article  CAS  Google Scholar 

  139. Hu JF, Liu YY, Yu YK, Zhao TZ, Liu SD, Wang QQ (1991) Diet and cancer of the colon and rectum: a case-control study in China. Int J Epidemiol 20:362–367

    Article  CAS  Google Scholar 

  140. Freudenheim JL, Graham S, Marshall JR, Haughey BP, Wilkinson G (1990) A case-control study of diet and rectal cancer in western New York. Am J Epidemiol 131:612–624

    CAS  Google Scholar 

  141. Franceschi S, Favero A, La Vecchia C, Negri E, Conti E, Montella M, Giacosa A, Nanni O, Decarli A (1997) Food groups and risk of colorectal cancer in Italy. Int J Cancer 72:56–61

    Article  CAS  Google Scholar 

  142. Erhardt JG, Meisner C, Bode JC, Bode C (2003) Lycopene, beta-carotene, and colorectal adenomas. Am J Clin Nutr 78:1219–1224

    CAS  Google Scholar 

  143. Nair S, Norkus EP, Hertan H, Pitchumoni CS (2001) Serum and colon mucosa micronutrient antioxidants: differences between adenomatous polyp patients and controls. Am J Gastroenterol 96:3400–3405

    Article  CAS  Google Scholar 

  144. Narisawa T, Fukaura Y, Hasebe M, Ito M, Aizawa R, Murakoshi M, Uemura S, Khachik F, Nishino H (1996) Inhibitory effects of natural carotenoids, α-carotene, ß-carotene, lycopene and lutein, on colonic aberrant crypt foci formation in rats. Cancer Lett 107:137–142

    Article  CAS  Google Scholar 

  145. Sengupta A, Ghosh S, Das RK, Bahattacharjee S, Bahattacharya S (2006) Chemopreventive potential of diallylsulfide, lycopene and theaflavin during chemically induced colon carcinogenesis in rat colon through modulation of cyclooxygenase–2 and inducible nitric oxide synthase pathways. Eur J Cancer Prev 15:301–305

    Article  CAS  Google Scholar 

  146. Kim JM, Araki S, Kim DJ, Park CB, Takasuka N, Baba-Toriyama H, Ota T, Nir Z, Khachik F, Shimdzu N, Tanaka Y, Osawa T, Uraji T, Murakoshi M, Nishino H, Tsuda H (1998) Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation. Carcinogenesis 19:81–85

    Article  CAS  Google Scholar 

  147. Wargovich MJ, Jimenez A, McKee K, Steele VE, Velasco M, Woods J, Price R, Gray K, Kelloff GJ (2000) Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression. Carcinogenesis 21:1149–1155

    Article  CAS  Google Scholar 

  148. Kim DJ, Takasuka N, Kim JM, Sekine K, Ota T, Asamoto M, Murakoshi M, Nishino H, Nir Z, Tsuda H (1997) Chemoprevention by lycopene of mouse lung neoplasia after combined initiation treatment with DEN, MNU and DMH. Cancer Lett 120:15–22

    Article  CAS  Google Scholar 

  149. Narisawa T, Hasebe M, Nomura S, Sakamoto H, Inakuma T, Ishiguro Y, Takayasu J, Nishino H (1998) Prevention of N-methylnitrosourea colon carcinogenesis in F344 rats by lycopene and tomato juice rich in lycopene. Jpn J Cancer Res 89:1003–1008

    Article  CAS  Google Scholar 

  150. Dias MC, Vieiralves NF, Gomes MI, Salvadori DM, Rodrigues MA, Barbisan LF (2010) Effects of lycopene, synbiotic and their association on early biomarkers of rat colon carcinogenesis. Food Chem Toxicol 48:772–780

    Article  CAS  Google Scholar 

  151. Tuzcu M, Aslan A, Tuzcu Z, Yabas M, Bahcecioglu IH, Ozercan IH, Kucuk O, Sahin K (2012) Tomato powder impedes the development of azoxhymethane-induced colorectal cancer in rats through suppression of COX–2 expression via NF-κB and regulating Nrf2/HO–1 pathway. Mol Nutr Food Res 56:1477–1481

    Article  CAS  Google Scholar 

  152. Tang FY, Pai MH, Wang XD (2011) Consumption of lycopene inhibits the growth and progression of colon cancer in a mouse xenograft model. J Agric Food Chem 59:9011–9021

    Article  CAS  Google Scholar 

  153. Steinmaus CM, Nunez S, Smith AH (2000) Diet and bladder cancer: a meta-analysis of six dietary variables. Am J Epidemiol 151:693–702

    Article  CAS  Google Scholar 

  154. Michaud DS, Pietinen P, Taylor PR, Virtanen M, Virtamo J, Albanes D (2002) Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study. Br J Cancer 87:960–965

    Article  CAS  Google Scholar 

  155. Zeegers MP, Goldbohm RA, van Den Brandt PA (2001) Consumption of vegetables and fruits and urothelial cancer incidence: a prospective study. Cancer Epidemiol Biomarkers Prev 10:1121–1128

    CAS  Google Scholar 

  156. Zeegers MP, Goldbohm RA, van den Brandt PA (2001) Are retinol, vitamin C, folate and carotenoids intake associated with bladder cancer risk? Results from the Netherlands Cohort Study. Br J Cancer 28:977–983

    Article  CAS  Google Scholar 

  157. Helzlsouer KJ, Comstock GW, Morris JS (1989) Selenium, lycopene, alpha-tocopherol, beta-carotene, retinol, and subsequent bladder cancer. Cancer Res 49:6144–6148

    CAS  Google Scholar 

  158. Hung RJ, Zhang ZF, Rao JY, Pantuck A, Reuter VE, Heber D, Lu QY (2006) Protective effects of plasma carotenoids on the risk of bladder cancer. J Urol 176:1192–1197

    Article  CAS  Google Scholar 

  159. Bruemmer B, White E, Vaughan TL, Cheney CL (1996) Nutrient intake in relation to bladder cancer among middle-aged men and women. Am J Epidemiol 144:485–495

    Article  CAS  Google Scholar 

  160. Riboli E, Gonzalez CA, Lopez-Abente G, Errezola M, Izarzugaza I, Escolar A, Nebot M, Hémon B, Agudo A (1991) Diet and bladder cancer in Spain: a multi-centre case-control study. Int J Cancer 49:214–219

    Article  CAS  Google Scholar 

  161. Nomura AM, Kolonel LN, Hankin JH, Yoshizawa CN (1991) Dietary factors in cancer of the lower urinary tract. Int J Cancer 48:199–205

    Article  CAS  Google Scholar 

  162. Okajima E, Ozono S, Endo T, Majima T, Tsutsumi M, Fukuda T, Akai H, Denda A, Hirao Y, Okajima E, Nishino H, Nir Z, Konishi Y (1997) Chemopreventive efficacy of piroxicam administered alone or in combination with lycopene and ß-carotene on the development of rat urinary bladder carcinoma after N-butyl-N-(4-hydroxybutyl) nitrosamine treatment. Jpn J Cancer Res 88:543–552

    Article  CAS  Google Scholar 

  163. Giovannucci E (1999) Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J Natl Cancer Inst 91:317–331

    Article  CAS  Google Scholar 

  164. Mayne ST, Cartmel B, Lin H, Zheng T, Goodwin WJ Jr (2004) Low plasma lycopene concentration is associated with increased mortality in a cohort of patients with prior oral, pharynx or larynx cancers. J Am Coll Nutr 23:34–42

    CAS  Google Scholar 

  165. Livny O, Kaplan I, Reifen R, Polak-Charcon S, Madar Z, Schwartz B (2002) Lycopene inhibits proliferation and enhances gap-junction communication of KB–1 human oral tumor cells. J Nutr 132:3754–3759

    CAS  Google Scholar 

  166. Negri E, Franceschi S, Bosetti C, Levi F, Conti E, Parpinel M, La Vecchia C (2000) Selected micronutrients and oral and pharyngeal cancer. Int J Cancer 86:122–127

    Article  CAS  Google Scholar 

  167. Zheng W, Blot WJ, Shu XO, Gao YT, Ji BT, Ziegler RG, Fraumeni JF Jr (1992) Diet and other risk factors for laryngeal cancer in Shangai, China. Am J Epidemiol 136:178–191

    CAS  Google Scholar 

  168. Franceschi S, Bidoli E, Baron AE, Barra S, Talamini R, Serraino D, La Vecchia C (1991) Nutrition and cancer of the oral cavity and pharynx in north-east Italy. Int J Cancer 47:20–25

    Article  CAS  Google Scholar 

  169. Zheng T, Boyle P, Willet WC, Hu H, Dan J, Evstifeeva TV, Niu S, MacMahon B (1993) A case-control study of oral cancer in Beijing, People’s Republic of China. Associations with nutrient intakes, foods and food groups. Eur J Cancer B Oral Oncol 29:45–55

    Article  Google Scholar 

  170. Bhuvaneswari V, Velmurugan B, Balasenthil S, Ramachandran CR, Nagini S (2001) Chemopreventive efficacy of lycopene on 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Fitoterapia 72:865–874

    Article  CAS  Google Scholar 

  171. Zakrzewska JM (2005) Oral lycopene—an efficacious treatment for oral leukoplakia? Evid Based Dent 6:17–18

    Article  Google Scholar 

  172. El-Rouby DH (2011) Histological and immunohistochemical evaluation of the chemopreventive role of lycopene in tongue carcinogenesis induced by 4-nitroquinoline–1-oxide. Arch Oral Biol 56:664–671

    Article  CAS  Google Scholar 

  173. Cheng HC, Chien H, Liao CH, Yang YY, Huang SY (2007) Carotenoids suppress proliferating cell nuclear antigen and cyclin D1 expression in oral carcinogenic models. J Nutr Biochem 18:667–675

    Article  CAS  Google Scholar 

  174. De Stefani E, Oreggia F, Boffetta P, Deneo-Pellegrini H, Ronco A, Mendilaharsu M (2000) Tomatoes, tomato-rich foods, lycopene and cancer of the upper aerodigestive tract: a case-control in Uruguay. Oral Oncol 36:47–53

    Article  Google Scholar 

  175. Giovannucci E, Clinton SK (1998) Tomatoes, lycopene, and prostate cancer. Proc Soc Exp Biol Med 218:129–139

    CAS  Google Scholar 

  176. Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, Stampfer MJ (1999) Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res 59:1225–1230

    CAS  Google Scholar 

  177. Giovannucci E, Ascherio A, Rimm EB, Stampfer MJ, Colditz GA, Willett WC (1995) Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 87:1767–1776

    Article  CAS  Google Scholar 

  178. Kelloff GJ, Lieberman R, Steele VE, Boone CW, Lubet RA, Kopelovitch L, Malone WA, Crowell JA, Sigman CC (1999) Chemoprevention of prostate cancer: concepts and strategies. Eur Urol 35:342–350

    Article  CAS  Google Scholar 

  179. Ozten-Kandaş N, Bosland MC (2011) Chemoprevention of prostate cancer: natural compounds, antiandrogens, and antioxidants – in vivo evidence. J Carcinog 10:27

    Article  CAS  Google Scholar 

  180. Etminan M, Takkouche B, Caamano-Isorna F (2004) The role of tomato products and lycopene in the prevention of prostate cancer: a meta-analysis of observational studies. Cancer Epidemiol Biomark Prev 13:340–345

    CAS  Google Scholar 

  181. Wei MY, Giovannucci EL (2012) Lycopene, tomato products, and prostate cancer incidence: a review and reassessment in the PSA screening era. J Oncol 2012:271063

    Article  CAS  Google Scholar 

  182. Ilic D, Misso M (2012) Lycopene for the prevention and treatment of benign prostatic hyperplasia and prostate cancer: a systematic review. Maturitas 72:269–276

    Article  CAS  Google Scholar 

  183. Jian L, Lee AH, Binns CW (2007) Tea and lycopene protect against prostate cancer. Asia Pac J Clin Nutr 16:453–457

    CAS  Google Scholar 

  184. Jain MG, Hislop GT, Howe GR, Ghadirian P (1999) Plant foods, antioxidants, and prostate cancer risk: findings from case, control studies in Canada. Nutr Cancer 34:173–184

    Article  CAS  Google Scholar 

  185. Beilby J, Ambrosini GL, Rossi E, De Klerk NH, Musk AW (2010) Serum levels of folate, lycopene, β-carotene, retinol and vitamin e and prostate cancer risk. Eur J Clin Nutr 64:1235–1238

    Article  CAS  Google Scholar 

  186. Kristal AR, Till C, Platz EA, Song X, King IB, Neuhouser ML, Ambrosone CB, Thompson IM (2011) Serum lycopene concentration and prostate cancer risk: results from the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev 20:638–646

    Article  CAS  Google Scholar 

  187. Clinton SK, Emenhiser C, Schwartz SJ, Bostwick DG, Williams AW, Moore BJ, Erdman JW Jr (1996) Cis-trans lycopene isomers, carotenoids and retinol in human prostate. Cancer Epidemiol Biomarkers Prev 5:823–833

    CAS  Google Scholar 

  188. Van Gils CH, Bostick RM, Stern MC, Taylor JA (2002) Differences in base excision repair capacity may modulate the effect of dietary antioxidant intake on prostate cancer risk: an example of polymorphisms in the XRCC1 gene. Cancer Epidemiol Biomarkers Prev 11:1279–1284

    Google Scholar 

  189. Kristal AR, Schenk MJ (2005) Directions for future epidemiological research in lycopene and prostate cancer risk. J Nutr 135:2037–2039

    Google Scholar 

  190. Ivanov NI, Cowell SP, Brown P, Rennie PS, Guns ES, Cox ME (2007) Lycopene differentially induces quiescence and apoptosis in androgen-responsive and -independent prostate cancer cell lines. Clin Nutr 26:252–263

    Article  CAS  Google Scholar 

  191. Tang L, Jin T, Zeng X, Wang JS (2005) Lycopene inhibits the growth of human androgen-independent prostate cancer cells in vitro and in BALB/c nude mice. J Nutr 135:287–290

    CAS  Google Scholar 

  192. Clinton SK (2005) Tomatoes or lycopene: a role in prostate carcinogenesis? J Nutr 135:2057–2059

    Google Scholar 

  193. Siler U, Herzog A, Spitzer V, Seifert N, Denelavas A, Hunziker P, Barella L, Hunziker W, Lein M, Goralczyk R, Wertz K (2005) Lycopene effects on rat normal prostate and prostate tumor tissue. J Nutr 135:2050–2052

    Google Scholar 

  194. Limpens J, Schroder FH, de Ridder CM, Bolder CA, Wildhagen MF, Obermuller-Jevic UC, Kramer K, van Weerden WM (2006) Combined lycopene and vitamin E treatment suppresses the growth of PC–346C human prostate cancer cells in nude mice. J Nutr 136:1287–1293

    CAS  Google Scholar 

  195. Boileau TW, Liao Z, Kim S, Lemeshow S, Erdman JW, Clinton SK (2003) Prostate carcinogenesis in N-methyl-N-nitrosurea (NMU)-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets. J Natl Cancer Inst 95:1578–1586

    Article  CAS  Google Scholar 

  196. Kucuk O, Sarkar F, Sakr W, Djuric Z, Khachik F, Pollak M, Bertram J, Grignon D, Banerjee M, Crissman J, Pontes E, Wood DP Jr (2001) Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev 10:861–868

    CAS  Google Scholar 

  197. Chen L, Stazewicz-Sapuntzakis M, Duncan C, Sharifi R, Ghosh L, vanBreemen R, Ashton D, Bowen PE (2001) Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention. J Natl Cancer Inst 93:1872–1879

    Article  CAS  Google Scholar 

  198. Ansari MS, Gupta NP (2003) A comparison of lycopene and orchidectomy vs orchidectomy alone in the management of advanced prostate cancer. BJU Int 92:375–378

    Article  CAS  Google Scholar 

  199. Mohanty NK, Saxena S, Singh UP, Goyal NK, Arora RP (2005) Lycopene as a chemopreventive agent in the treatment of high grade prostatic intraepithelial neoplasia. Urol Oncol 23:383–385

    Article  CAS  Google Scholar 

  200. Edinger MS, Koff WJ (2006) Effect of the consumption of tomato paste on plasma prostate specific antigen levels in patients with benign prostate hyperplasia. Braz J Med Biol Res 39:1115–1119

    Article  CAS  Google Scholar 

  201. Clark PE, Hall MC, Borden LS Jr, Miller AA, Hu JJ, Lee WR, Stindt D, D’Agostino R Jr, Lovato J, Harmon M, Torti FM (2006) Phase I-II prospective dose escalating trial of lycopene in patients with biochemical relapse of prostate cancer after definitive local therapy. Urology 67:1257–1261

    Article  Google Scholar 

  202. Chang S, Erdman JW, Clinton SK, Vadiveloo M, Strom SS, Yamamura Y, Duphorne CM, Spitz MR, Amos CI, Contois JH, Gu X, Babaian RJ, Scardino PT, Hursting SD (2005) Relationship between plasma carotenoids and prostate cancer. Nutr Cancer 53:127–134

    Article  CAS  Google Scholar 

  203. Vogt TM, Mayne ST, Graubard BI, Swanson CA, Sowell AL, Schoenberg JB, Swanson GM, Greenberg RS, Hoover RN, Hayes RB, Ziegler RG (2002) Serum lycopene, other serum carotenoids, and risk of prostate cancer in US Blacks and Whites. Am J Epidemiol 155:1023–1032

    Article  CAS  Google Scholar 

  204. Van Breemen RB, Sharifi R, Viana M, Pajkovic N, Zhu D, Yuan L, Yang Y, Bowen PE, Stacewicz-Sapuntzakis M (2011) Antioxidant effects of lycopene in African American men with prostate cancer or benign prostate hyperplasia: a randomized, controlled trial. Cancer Prev Res (Phila) 4:711–718

    Article  CAS  Google Scholar 

  205. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics. CA Cancer J Clin 60:277–300

    Article  Google Scholar 

  206. Faramawi MF, Johnson E, Fry MW, Sall M, Zhou Y (2007) Consumption of different types of meat and the risk of renal cancer: meta-analysis of case-control studies. Cancer Causes Control 18:125–133

    Article  Google Scholar 

  207. Maclure M, Willet W (1990) A case–control study of diet and risk of renal adenocarcinoma. Epidemiology 1:430–440

    Article  CAS  Google Scholar 

  208. Lindblad P, Wolk A, Bergstrom R, Adami HO (1997) Diet and risk of renal cell cancer: a population-based case–control study. Cancer Epidemiol Biomarkers Prev 6:215–223

    CAS  Google Scholar 

  209. Mellemgaard A, McLaughlin JK, Overvad K, Olsen JH (1996) Dietary risk factors for renal cell carcinoma in Demark. Eur J Cancer 4:673–682

    Article  Google Scholar 

  210. Talamini R, Baron AE, Barra S, Bidoli E, La Vecchia C, Negri E, Serraino D, Franceschi S (1990) A case–control study of risk factors for renal cell cancer in northern Italy. Cancer Causes Control 1:125–131

    Article  CAS  Google Scholar 

  211. Cross B, Sahin K, Sahin N, Ciccone K, Osunkoya A, Master V, Harris W, Carthon B, Mohammad R, Bilir B, Canter D, Wertz K, Wu DQ, Moreno C, Walker C, Kucuk O (2012) Lycopene in the prevention of renal cell cancer in the TSC2 mutant Eker rat model. J Urol 187:63–63

    Article  Google Scholar 

  212. Zhao SZ, Wong JM, Arguelles LM (1999) Hospitalization costs associated with leiomyoma. Clin Ther 21:563–575

    Article  CAS  Google Scholar 

  213. Terry KL, Missmer SA, Hankinson SE, Willett WC, De Vivo I (2008) Lycopene and other carotenoid intake in relation to risk of uterine leiomyomata. Am J Obstet Gynecol 198:37.e1–8

    Article  CAS  Google Scholar 

  214. Stewart EA (2001) Uterine fibroids. Lancet 357:293–298

    Article  CAS  Google Scholar 

  215. Moore AB, Castro L, Yu L, Zheng X, Di X, Sifre MI, Kissling GE, Newbold RR, Bortner CD, Dixon D (2007) Stimulatory and inhibitory effects of genistein on human uterine leiomyoma cell proliferation are influenced by the concentration. Hum Reprod 22:2623–2631

    Article  CAS  Google Scholar 

  216. Sahin K, Ozercan R, Onderci M, Sahin N, Gursu MF, Khachik F, Sarkar FH, Munkarah A, Ali-Fehmi R, Kmak D, Kucuk O (2004) Lycopene supplementation prevents the development of spontaneous smooth muscle tumors of the oviduct in Japanese quail. Nutr Cancer 50:181–189

    Article  CAS  Google Scholar 

  217. Sahin N, Cross B, Sahin K, Ciccone K, Osunkoya A, Master V, Haris W, Carthon B, Mohammad R, Moreno C, Walker C, Kucuk O (2011) Preventıon of uterine leiomyoma by lycopene in the TSC2 mutant eker rat model. In: Fourth international congress on nutrition and cancer, Antalya, 19–23 Oct 2011

    Google Scholar 

  218. Conklin KA (2000) Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr Cancer 37:1–18

    Article  CAS  Google Scholar 

  219. Sahin K, Sahin N, Kucuk O (2010) Lycopene and chemotherapy toxicity. Nutr Cancer 62:988–995

    Article  CAS  Google Scholar 

  220. Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB (2008) Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst 100:773–783

    Article  CAS  Google Scholar 

  221. Sahin K, Tuzcu M, Sahin N, Ali S, Kucuk O (2010) Nrf2/HO–1 signaling pathway may be the prime target for chemoprevention of cisplatin-induced nephrotoxicity by lycopene. Food Chem Toxicol 48:2670–2674

    Article  CAS  Google Scholar 

  222. Erhola M, Kellokumpu-Lehtinen P, Metsa-Ketela T, Alanko K, Nieminen MM (1996) Effects of anthracyclin-based chemotherapy on total plasma antioxidant capacity in small cell lung cancer patients. Free Radic Biol Med 21:383–390

    Article  CAS  Google Scholar 

  223. Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C (2008) Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. Int J Cancer 123:1227–1239

    Article  CAS  Google Scholar 

  224. D'Incalci M, Steward WP, Gescher AJ (2007) Modulation of response to cancer chemotherapeutic agents by diet constituents: is the available evidence sufficiently robust for rational advice for patients? Cancer Treat Rev 33:223–229

    Article  CAS  Google Scholar 

  225. Dogukan A, Tuzcu M, Agca CA, Gencoglu H, Sahin N, Onderci M, Ozercan IH, Ilhan N, Kucuk O, Sahin K (2011) A tomato lycopene complex protects the kidney from cisplatin-induced injury via affecting oxidative stress as well as Bax, Bcl–2, and HSPs expression. Nutr Cancer 63:427–434

    Article  CAS  Google Scholar 

  226. Rios AO, Antunes LMG, Bianchi MLP (2009) Bixin and lycopene modulation of free radical generation induced by cisplatin–DNA interaction. Food Chem 113:1113–1118

    Article  CAS  Google Scholar 

  227. Zhou C, Han W, Zhang P, Cai M, Wei D, Zhang C (2008) Lycopene from tomatoes partially alleviates the bleomycin-induced experimental pulmonary fibrosis in rats. Nutr Res 28:122–130

    Article  CAS  Google Scholar 

  228. Ferreira AL, Salvadori DM, Nascimento MC, Rocha NS, Correa CR, Pereira EJ, Matsubara LS, Matsubara BB, Ladeira MS (2007) Tomato-oleoresin supplement prevents doxorubicin-induced cardiac myocyte oxidative DNA damage in rats. Mutat Res 631:26–35

    Article  CAS  Google Scholar 

  229. Sendão MC, Behling EB, dos Santos RA, Antunes LM, de Lourdes Pires Bianchi M (2006) Comparative effects of acute and subacute lycopene administration on chromosomal aberrations induced by cisplatin in male rats. Food Chem Toxicol 44:1334–1339

    Article  CAS  Google Scholar 

  230. Karimi G, Ramezani M, Abdi A (2005) Protective effects of lycopene and tomato extract against doxorubicin-induced cardiotoxicity. Phytother Res 19:912–914

    Article  CAS  Google Scholar 

  231. Puri T, Goyal S, Julka PK, Nair O, Sharma DN, Rath GK (2010) Lycopene in treatment of high-grade gliomas: a pilot study. Neurol India 58:20–23

    Article  Google Scholar 

  232. Andic F, Garipagaoglu M, Yurdakonar E, Tuncel N, Kucuk O (2009) Lycopene in the prevention of gastrointestinal toxicity of radiotherapy. Nutr Cancer 61:784–788

    Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Prof. Dr. Nurhan Sahin, Dr. Mehmet Tuzcu, and Dr. Cemal Orhan for much valuable collaboration.

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Authors and Affiliations

  1. Department of Animal Nutrition, Firat University, Elazig, 23119, Turkey

    Prof. Kazim Sahin DVM, Ph.D. (Faculty of Veterinary Medicine)

  2. Emory University, Winship Cancer Institute, Atlanta, GA, USA

    Omer Kucuk

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  1. Prof. Kazim Sahin DVM, Ph.D.
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  2. Omer Kucuk
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Correspondence to Kazim Sahin DVM, Ph.D. .

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Editors and Affiliations

  1. Botany Department, M.L. Sukhadia University, Durga Nursery Road, Udaipur, 313001, Rajasthan, India

    Kishan Gopal Ramawat

  2. Institute of Vine and Wine Sciences, Biological-Active Plant Substances Study, University of Bordeaux, 210 Chemin de Leysotte CS 50008, Villenave d'Ornon, 33882, France

    Jean-Michel Mérillon

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Sahin, K., Kucuk, O. (2013). Lycopene in Cancer Prevention. In: Ramawat, K., Mérillon, JM. (eds) Natural Products. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-22144-6_164

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