Anticancer Properties of Lycopene

  • Kazim SahinEmail author
  • Cemal Orhan
  • Nurhan Sahin
  • Omer Kucuk
Reference work entry
Part of the Reference Series in Phytochemistry book series (RSP)


Lycopene is an acyclic isomer of beta-carotene, found in red-colored fruits and vegetables, including tomatoes, and their processed products, watermelon, papaya, guava, carrots, red grapefruit, and sweet potatoes. It is synthesized by plants or autotrophic bacteria but not by animals. This work provides an up-to-date overview of mechanisms linking lycopene in the human diet and cancer, considering epidemiological, clinical studies, and experimental data. Dietary lycopene supplementation may reduce the risk of cancers of many organs such as prostate and at the same time retard the growth of tumors. The main protection properties of lycopene against cancer include antioxidant, anti-inflammatory, anti-inhibitory of cancer cell proliferation, anti-apoptotic, increased gap-junctional communication, interferences in insulin-like growth factor 1 receptor signaling pathways, and cell cycle progression and, the ability to improve the metabolic profile. In this context, lycopene has been shown to exert a protective effect in humans or animals with cancers including prostate, breast, gastric, colon, pancreatic, renal, and several other cancers in many studies, although the obtained results are sometimes inconsistent, which warrants further studies focusing on its bioactivity. In this chapter, lycopene supplementation in cancer prevention is reviewed and possible mechanisms of action are discussed in detail.


Cancer Nutrition Prevention Lycopene Molecular mechanism 







ATP-binding cassette transporter 1


Aberrant crypt foci




Antioxidant response element


Breast cancer




Cyclin-dependent kinases


Confidence interval




Connexin 43








Extracellular signal-regulated kinase 1


Gap-junctional intercellular communication


Glycogen synthase kinase-3β


Hepatocellular carcinoma


Human hepatocellular liver carcinoma cell line


High-fat diet


Insulin-like growth factor


Insulin like growth factor binding protein 3


Inducible nitric oxide synthase


Kelch-like ECH-associated protein 1-


Liver X receptor alpha


Human breast adenocarcinoma cell line


Matrix metalloproteinase 2


Matrix metalloproteinase 7


Matrix metalloproteinase 9




Nicotinamide adenine dinucleotide phosphate


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




Nuclear factor-E2-related factor 2


Odds ratios


Polychlorinated biphenyls


Proliferating cellular nuclear antigen


Phosphorylated mammalian target of rapamycin


Peroxisome proliferator-activated receptor gamma


Prostate-specific antigen


Renal cell carcinoma


Reduction oxidative stress


Superoxide dismutase


Tumor necrosis factor-alpha



The study was supported in part by Turkish Academy of Sciences (KS).


  1. 1.
    National Research Council (US) Committee on Diet and Health (1989) Diet and health: Implications for reducing chronic disease risk. The National Academies Press, Washington, DCGoogle Scholar
  2. 2.
    American Cancer Society (1984) Nutrition and cancer: Causation and prevention. An American Cancer Society special report. CA Cancer J Clin 34:5–10Google Scholar
  3. 3.
    Lee BM, Park KK (2003) Beneficial and adverse effects of chemopreventive agents. Mutat Res 523–524:265–278CrossRefGoogle Scholar
  4. 4.
    Tanaka T, Shinimizu M, Moriwaki H (2012) Cancer chemoprevention by carotenoids. Molecules 17:3202–3242. Scholar
  5. 5.
    Palozza P, Simone R, Catalano A, Russo M, Bohm V (2012) Lycopene modulation of molecular targets affected by smoking exposure. Curr Cancer Drug Targets 12:640–657. Scholar
  6. 6.
    Sahin K, Orhan C, Tuzcu M, Sahin N, Ali S, Bahcecioglu IH, Guler O, Ozercan I, Ilhan N, Kucuk O (2014) Orally administered lycopene attenuates diethylnitrosamine-induced hepatocarcinogenesis in rats by modulating Nrf-2/HO-1 and Akt/mTOR pathways. Nutr Cancer 66:590–598. Scholar
  7. 7.
    Nguyen ML, Schwartz SJ (1999) Lycopene: Chemical and biological properties. Food Technol 53:38–45Google Scholar
  8. 8.
    Gupta S, Jawanda MK, Arora V, Mehta N, Yadav V (2015) Role of lycopene in preventing oral diseases as a nonsurgical aid of treatment. Int J Prev Med 6:70. Scholar
  9. 9.
    Ascenso A, Ribeiro H, Marques HC, Oliveira H, Santos C, Simões S (2014) Chemoprevention of photocarcinogenesis by lycopene. Exp Dermatol 23:874–878. Scholar
  10. 10.
    Olson JA, Krinsky NI (1995) Introduction: the colorful, fascinating world of the carotenoids: important physiologic modulators. FASEB J 9:1547–1550CrossRefGoogle Scholar
  11. 11.
    van Breemen RB, Pajkovic N (2008) Multitargeted therapy of cancer by lycopene. Cancer Lett 269:339–351. Scholar
  12. 12.
    Di Mascio P, Kaiser S, Sies H (1989) Lycopene as the most effective biological carotenoid singlet oxygen quencher. Arch Biochem Biophys 274:532–538CrossRefGoogle Scholar
  13. 13.
    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. Scholar
  14. 14.
    Giovannucci E (2002) A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer. Exp Biol Med 227:852–859CrossRefGoogle Scholar
  15. 15.
    Schierle J, Bretzel W, Buhler I, Faccin N, Hess D, Steiner K, Schuep W (1997) Content and isomeric ratio of lycopene in food and human blood plasma. Food Chem 59:459–565CrossRefGoogle Scholar
  16. 16.
    Viuda-Martos M, Sanchez-Zapata E, Sayas-Barberá E, Sendra E, Pérez-Álvarez JA, Fernández-López J (2014) Tomato and tomato byproducts. Human health benefits of lycopene and its application to meat products: a review. Crit Rev Food Sci Nutr 54(8):1032–1049. Scholar
  17. 17.
    Kong KW, Khoo HE, Prasad KN, Ismail A, Tan CP, Rajab NF (2010) Revealing the power of the natural red pigment lycopene. Molecules 15:959–987. Scholar
  18. 18.
    Bowen P, Chen L, Stacewicz-Sapuntzakis M, Duncan C, Sharifi R, Ghosh L, Kim HS, Christov-Tzelkov K, van Breemen R (2002) Tomato sauce supplementation and prostate cancer: lycopene accumulation and modulation of biomarkers of carcinogenesis. Exp Biol Med (Maywood) 227:886–893CrossRefGoogle Scholar
  19. 19.
    Porrini M, Riso P (2000) Lymphocyte lycopene concentration and DNA protection from oxidative damage is increased in women after a short period of tomato consumption. J Nutr 130:189–192. Scholar
  20. 20.
    Agarwal S, Rao AV (1998) Tomato lycopene and low density lipoprotein oxidation: a human dietary intervention study. Lipids 33:981–984CrossRefGoogle Scholar
  21. 21.
    Sahin K, Orhan C, Tuzcu M, Sahin N, Hayirli A, Bilgili S, Kucuk O (2016) Lycopene activates antioxidant enzymes and nuclear transcription factor systems in heat-stressed broilers. Poult Sci 95:1088–1095. Scholar
  22. 22.
    Pereira BLB, Reis PP, Severino FE, Felix TF, Braz MG, Nogueira FR, Silva RAC, Cardoso AC, Lourenco MAM, Figueiredo AM, Chiuso-Minicucci F, Azevedo PS, Polegato BF, Okoshi K, Fernandes AAH, Paiva SAR, Zornoff LAM, Minicucci MF (2017) Tomato (Lycopersicon esculentum) or lycopene supplementation attenuates ventricular remodeling after myocardial infarction through different mechanistic pathways. J Nutr Biochem 46:117–124. Scholar
  23. 23.
    Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 97:55–74. Scholar
  24. 24.
    Sahin K, Tuzcu M, Sahin N, Ali S, Kucuk O (2010 Oct) Nrf2/HO-1 signaling pathway may be the prime target for chemoprevention of cisplatin-induced nephrotoxicity by lycopene. Food Chem Toxicol 48(10):2670–2674. Scholar
  25. 25.
    Mein JR, Lian F, Wang XD (2008) Biological activity of lycopene metabolites: implications for cancer prevention. Nutr Rev 66:667–683. Scholar
  26. 26.
    Bertram JS (1999) Carotenoids and gene regulation. Nutr Rev 57:182–191CrossRefGoogle Scholar
  27. 27.
    Zhang LX, Cooney RV, Bertram JS (1992) Carotenoids up-regulate connexin 43 gene expression independent of their pro-vitamin A or antioxidant properties. Cancer Res 52:5707–5712PubMedGoogle Scholar
  28. 28.
    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. Scholar
  29. 29.
    Neveu M, Bertram JS (2000) Gap junctions and neoplasia. In: Hetzberg EL, Bittar EE (eds) Gap Junctions. JAI Press, Greenwich, pp 221–262CrossRefGoogle Scholar
  30. 30.
    Lee SW, Tomasetto C, Sager R (1991) Positive selection of candidate tumor suppressor genes by subtractive hybridization. Proc Natl Acad Sci U S A 88:2825–2829CrossRefGoogle Scholar
  31. 31.
    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.<446::AID-IJC10>3.0.CO;2-4CrossRefPubMedGoogle Scholar
  32. 32.
    Stahl W, von Laar J, Martin HD, Emmerich T, Sies H (2000) Stimulation of gap junctional communication: comparison of acyclo-retinoic acid and lycopene. Arch Biochem Biophys 373:271–274. Scholar
  33. 33.
    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. Scholar
  34. 34.
    Erdman JW Jr, Ford NA, Lindshield BL (2009) Are the health attributes of lycopene related to its antioxidant function? Arch Biochem Biophys 483:229–235. Scholar
  35. 35.
    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. Scholar
  36. 36.
    Assar EA, Vidalle MC, Chopra M, Hafizi S (2016) Lycopene acts through inhibition of IκB kinase to suppress NF-κB signaling in human prostate and breast cancer cells. Tumor Biol 37:9375–9385. Scholar
  37. 37.
    Trejo-Solís C, Pedraza-Chaverrí J, Torres-Ramos M, Jiménez-Farfán D, Cruz Salgado A, Serrano-García N, Osorio-Rico L, Sotelo J (2013) Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition. Evid Based Complement Alternat Med 2013:705121. Scholar
  38. 38.
    Kelkel M, Schumacher M, Dicato M, Diederich M (2011) Antioxidant and anti-proliferative properties of lycopene. Free Radic Res 45:925–940. Scholar
  39. 39.
    Nahum A, Zeller L, Danilenko M, Prall OW, Watts CK, Sutherland RL, Levy J, Sharoni Y (2006) Lycopene inhibition of IGF-induced cancer cell growth depends on the level of cyclin D1. Eur J Nutr 45:275–282. Scholar
  40. 40.
    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. Scholar
  41. 41.
    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. Scholar
  42. 42.
    Simone RE, Russo M, Catalano A, Giovanni M, Kati F, Volker B, Paola P (2011) Lycopene inhibits NF-KB-Mediated IL-8 expression and changes redox and PPARγ signalling in cigarette smoke-stimulated macrophages. PLoS One 6(5):e19652. Scholar
  43. 43.
    Feng D, Ling WH, Duan RD (2010) Lycopene suppresses LPS-induced NO and IL-6 production by inhibiting the activation of ERK, p38MAPK, and NF-κB in macrophages. Inflamm Res 59:115–121. Scholar
  44. 44.
    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. Scholar
  45. 45.
    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. Biorg Medicinal Chem 14:6859–6867. Scholar
  46. 46.
    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. Scholar
  47. 47.
    Bae JM (2016) Reinterpretation of the results of a pooled analysis of dietary carotenoid intake and breast cancer risk by using the interval collapsing method. Epidemiol Health 38:e2016024. Scholar
  48. 48.
    Dos Santos RC, Ombredane AS, Souza JMT, Vasconcelos AG, Plácido A, Amorim ADGN, Barbos EA, Lima FCDA, Ropke CD, Alves MMM, Arcanjo DDR, Carvalho FAA, Delerue-Matos C, Joanitti GA, Leite JRSA (2018) Lycopene-rich extract from red guava (Psidium guajava L.) displays cytotoxic effect against human breast adenocarcinoma cell line MCF-7 via an apoptotic-like pathway. Food Res Int 105:184–196. Scholar
  49. 49.
    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. Scholar
  50. 50.
    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. Zhonghua Yu Fang Yi Xue Za Zhi 36:254–257PubMedGoogle Scholar
  51. 51.
    Peng SJ, Li J, Zhou Y, Tuo M, Qin XX, Yu Q, Cheng H, Li YM (2017) In vitro effects and mechanisms of lycopene in MCF-7 human breast cancer cells. Genet Mol Res 16:1–8. Scholar
  52. 52.
    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. Scholar
  53. 53.
    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 21:118–123PubMedGoogle Scholar
  54. 54.
    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. Scholar
  55. 55.
    Singh A, Neupane YR, Panda BP, Kohli K (2017) Lipid Based nanoformulation of lycopene improves oral delivery: formulation optimization, ex vivo assessment and its efficacy against breast cancer. J Microencapsul 34:416–429. Scholar
  56. 56.
    Eliassen AH, Hendrickson SJ, Brinton LA, Buring JE, Campos H, Dai Q, Dorgan JF, Franke AA, Gao YT, Goodman MT, Hallmans G, Helzlsouer KJ, Hoffman-Bolton J, Hultén K, Sesso HD, Sowell AL, Tamimi RM, Toniolo P, Wilkens LR, Winkvist A, Zeleniuch-Jacquotte A, Zheng W, Hankinson SE (2012) Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies. J Natl Cancer Inst 104:1905–1916. Scholar
  57. 57.
    Sesso HD, Buring JE, Zhang SM, Norkus EP, Gaziano JM (2005) Dietary and plasma lycopene and the risk of breast cancer. Cancer Epidemiol Biomark Prev 14:1074–1081. Scholar
  58. 58.
    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. Scholar
  59. 59.
    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 Biomark Prev 11:451–457Google Scholar
  60. 60.
    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. Scholar
  61. 61.
    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. Scholar
  62. 62.
    Männistö S, Smith-Warner SA, Spiegelman D, Albanes D, Anderson K, van den Brandt PA, Cerhan JR, Colditz G, Feskanich D, Freudenheim JL, Giovannucci E, Goldbohm RA, Graham S, Miller AB, Rohan TE, Virtamo J, Willett WC, Hunter DJ (2004) Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies. Cancer Epidemiol Biomark Prev 13:40–48CrossRefGoogle Scholar
  63. 63.
    Asbaghi S, Saedisomeolia A, Hosseini M, Honarvar NM, Khosravi A, Azargashb E (2015) Dietary Intake and Serum Level of Carotenoids in Lung Cancer Patients: A Case-Control Study. Nutr Cancer 67:893–898. Scholar
  64. 64.
    Palozza P, Simone RE, Catalano A, Mele MC (2011) Tomato lycopene and lung cancer prevention: from experimental to human studies. Cancers (Basel) 3:2333–2357. Scholar
  65. 65.
    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. Scholar
  66. 66.
    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. Scholar
  67. 67.
    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. Scholar
  68. 68.
    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 156:536–547CrossRefGoogle Scholar
  69. 69.
    Graham DL, Carail M, Caris-Veyrat C, Lowe GM (2010) Cigarette smoke and human plasma lycopene depletion. Food Chem Toxicol 48:2413–2420. Scholar
  70. 70.
    Shareck M, Rousseau MC, Koushik A, Siemiatycki J, Parent ME (2017) Inverse association between dietary intake of selected carotenoids and vitamin C and risk of lung cancer. Front Oncol 7:23. Scholar
  71. 71.
    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. Scholar
  72. 72.
    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 94:57–63CrossRefGoogle Scholar
  73. 73.
    Satia JA, Littman A, Slatore CG, Galanko JA, White E (2009) Long-term use of beta-carotene, retinol, lycopene, and lutein supplements and lung cancer risk: results from the VITamins and Lifestyle (VITAL) study. Am J Epidemiol 169:815–828. Scholar
  74. 74.
    Liu C, Russell RM (2008) Nutrition and gastric cancer risk: an update. Nutr Rev 66:237–249. Scholar
  75. 75.
    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 Shanghai, China. Cancer Epidemiol Biomark Prev 11(Pt 1):1772–1780Google Scholar
  76. 76.
    Velmurugan B, Bhuvaneswari V, Nagini S (2001) Lycopene, an antioxidant carotenoid modulates glutathione-dependent hepatic biotransformation enzymes during experimental gastric carcinogenesis. Nutr Res 8:1117–1124. Scholar
  77. 77.
    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 14:387–293CrossRefGoogle Scholar
  78. 78.
    Zhou S, Zhang R, Bi T, Lu Y, Jiang L (2016) Inhibitory effect of lycopene against the growth of human gastric cancer cells. Afr J Tradit Complement Altern Med 13:184–190. Scholar
  79. 79.
    Nouraie M, Pietinen P, Kamangar F, Dawsey SM, Abnet CC, Albanes D, Virtamo J, Taylor PR (2005) Fruits, vegetables, and antioxidants and risk of gastric cancer among male smokers. Cancer Epidemiol Biomark Prev 14:2087–2092. Scholar
  80. 80.
    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. Scholar
  81. 81.
    De Stefani E, Boffetta P, Brennan P, Deneo-Pellegrini H, Carzoglio JC, Ronco A, Mendilaharsu M (2000) Dietary carotenoids and risk of gastric cancer: a case-control study in Uruguay. Eur J Cancer Prev 9:329–334CrossRefGoogle Scholar
  82. 82.
    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. Scholar
  83. 83.
    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 59:181–184CrossRefGoogle Scholar
  84. 84.
    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 Biomark Prev 13:1772–1780Google Scholar
  85. 85.
    Zhou Y, Wang T, Meng Q, Zhai S (2016) Association of carotenoids with risk of gastric cancer: A meta-analysis. Clin Nutr 35:109–116. Scholar
  86. 86.
    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. Scholar
  87. 87.
    Rawat D, Shrivastava S, Naik RA, Chhonker SK, Mehrotra A, Koiri RK (2018) An overview of natural plant products in the treatment of hepatocellular carcinoma. Anti Cancer Agents Med Chem.
  88. 88.
    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. Scholar
  89. 89.
    Bosch FX, Ribes J, Diaz M, Cleries R (2004) Primary liver cancer: worldwide incidence and trends. Gastroenterology 127:5–16CrossRefGoogle Scholar
  90. 90.
    Kataria Y, Deaton RJ, Enk E, Jin M, Petrauskaite M, Dong L, Goldenberg JR, Cotler SJ, Jensen DM, van Breemen RB, Gann PH (2016) Retinoid and carotenoid status in serum and liver among patients at high-risk for liver cancer. BMC Gastroenterol 16:30. Scholar
  91. 91.
    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. Scholar
  92. 92.
    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. Scholar
  93. 93.
    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 4:177–186PubMedGoogle Scholar
  94. 94.
    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 19:403–411CrossRefGoogle Scholar
  95. 95.
    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. Scholar
  96. 96.
    Jhou BY, Song TY, Lee I, Hu ML, Yang NC (2017) Lycopene Inhibits Metastasis of Human Liver Adenocarcinoma SK-Hep-1 Cells by Downregulation of NADPH Oxidase 4 Protein Expression. J Agric Food Chem 65:6893–6903. Scholar
  97. 97.
    Astorg P, Gradelet S, Berges R, Suschetet M (1997) Dietary lycopene decreases the initiation of liver preneoplastic foci by diethylnitrosamine in the rat. Nutr Cancer 29:60–68. Scholar
  98. 98.
    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. Scholar
  99. 99.
    Cheng J, Miao B, Hu KQ, Fu X, Wang XD (2018) Apo-10′-lycopenoic acid inhibits cancer cell migration and angiogenesis and induces peroxisome proliferator-activated receptor γ. J Nutr Biochem 56:26–34. Scholar
  100. 100.
    Aizawa K, Liu C, Tang S, Veeramachaneni S, Hu KQ, Smith DE, Wang XD (2016) Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation. Int J Cancer 139:1171–1181. Scholar
  101. 101.
    Ip BC, Liu C, Ausman LM, von Lintig J, Wang XD (2014) Lycopene attenuated hepatic tumorigenesis via differential mechanisms depending on carotenoid cleavage enzyme in mice. Cancer Prev Res (Phila) 7:1219–1227. Scholar
  102. 102.
    Bhatia N, Gupta P, Singh B, Koul A (2015) Lycopene Enriched Tomato Extract Inhibits Hypoxia, Angiogenesis, and Metastatic Markers in early Stage N-Nitrosodiethylamine Induced Hepatocellular Carcinoma. Nutr Cancer 67:1268–1275. Scholar
  103. 103.
    Jeurnink SM, Ros MM, Leenders M, van Duijnhoven FJ, Siersema PD, Jansen EH, van Gils CH, Bakker MF, Overvad K, Roswall N, Tjønneland A, Boutron-Ruault MC, Racine A, Cadeau C, Grote V, Kaaks R, Aleksandrova K, Boeing H, Trichopoulou A, Benetou V, Valanou E, Palli D, Krogh V, Vineis P, Tumino R, Mattiello A, Weiderpass E, Skeie G, Castaño JM, Duell EJ, Barricarte A, Molina-Montes E, Argüelles M, Dorronsoro M, Johansen D, Lindkvist B, Sund M, Crowe FL, Khaw KT, Jenab M, Fedirko V, Riboli E, Bueno-de-Mesquita HB (2015) Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European prospective investigation into cancer and nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk. Int J Cancer 136:E665–E676. Scholar
  104. 104.
    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. Scholar
  105. 105.
    Donaldson MS (2004) Nutrition and cancer: a review of the evidence for an anti-cancer diet. Nutr J 3:19. Scholar
  106. 106.
    McCullough ML, Giovannucci EL (2004) Diet and cancer prevention. Oncogene 23:6349–6364. Scholar
  107. 107.
    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. Scholar
  108. 108.
    Huang X, Gao Y, Zhi X, Ta N, Jiang H, Zheng J (2016) Association between vitamin A, retinol and carotenoid intake and pancreatic cancer risk: Evidence from epidemiologic studies. Sci Rep 6:38936. Scholar
  109. 109.
    Wang Y, Cui R, Xiao Y, Fang J, Xu Q (2015) Effect of carotene and lycopene on the risk of prostate cancer: A systematic review and dose-response meta-analysis of observational studies. PLoS One 10:e0137427. Scholar
  110. 110.
    Burney PG, 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. Scholar
  111. 111.
    Kim MJ, Kim H (2015) Anticancer effect of lycopene in gastric carcinogenesis. J Cancer Prev 20:92–96. Scholar
  112. 112.
    Wang X, Yang HH, Liu Y, Zhou Q, Chen ZH (2016) Lycopene consumption and risk of colorectal cancer: A meta-analysis of observational studies. Nutr Cancer 68:1083–1096. Scholar
  113. 113.
    Teodoro AJ, Oliveira FL, Martins NB, Maia Gde A, Martucci RB, Borojevic R (2012) Effect of lycopene on cell viability and cell cycle progression in human cancer cell lines. Cancer Cell Int 12:36. Scholar
  114. 114.
    Huang RF, Wei YJ, Inbaraj BS, Chen BH (2015) Inhibition of colon cancer cell growth by nanoemulsion carrying gold nanoparticles and lycopene. Int J Nanomedicine 10:2823–2846. Scholar
  115. 115.
    Tuzcu M, Aslan A, Tuzcu Z, Yabas M, Bahcecioglu IH, Ozercan IH, Kucuk O, Sahin K (2012) Tomato powder impedes the development of azoxymethane-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. Scholar
  116. 116.
    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 59:9011–9021CrossRefGoogle Scholar
  117. 117.
    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 120:15–22CrossRefGoogle Scholar
  118. 118.
    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 89:1003–1008CrossRefGoogle Scholar
  119. 119.
    Erhardt JG, Meisner C, Bode JC (2003) Lycopene, beta-carotene, and colorectal adenomas. Am J Clin Nutr 78:1219–1224. Scholar
  120. 120.
    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. Scholar
  121. 121.
    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 20:362–367CrossRefGoogle Scholar
  122. 122.
    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 131:612–624CrossRefGoogle Scholar
  123. 123.
    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 72:56–61CrossRefGoogle Scholar
  124. 124.
    Stahl W, Sies H (2012) Photoprotection by dietary carotenoids: concept, mechanisms, evidence and future development. Mol Nutr Food Res 56:287–295. Scholar
  125. 125.
    Stahl W, Sies H (2007) Carotenoids and flavonoids contribute to nutritional protection against skin damage from sunlight. Mol Biotechnol 37:26–30CrossRefGoogle Scholar
  126. 126.
    Wright TI, Spencer JM, Flowers FP (2006) Chemoprevention of nonmelanoma skin cancer. J Am Acad Dermatol 54:933–946. Scholar
  127. 127.
    Ascenso A, Pedrosa T, Pinho S, Pinho F, de Oliveira JM, Cabral Marques H, Oliveira H, Simões S, Santos C (2016) The effect of lycopene preexposure on UV-B-Irradiated human keratinocytes. Oxidative Med Cell Longev 2016:8214631. Scholar
  128. 128.
    Ribaya-Mercado JD, Garmyn M, Gilchrest BA, Russell RM (1995) Skin lycopene is destroyed preferentially over beta-carotene during ultraviolet irradiation in humans. J Nutr 125:1854–1859. Scholar
  129. 129.
    Stahl W, Heinrich U, Wiseman S, Eichler O, Sies H, Tronnier H (2001) Dietary tomato paste protects against ultraviolet light-induced erythema in humans. J Nutr 131:1449–1451. Scholar
  130. 130.
    Stahl W, Heinrich U, Aust O, Tronnier H, Sies H (2006) Lycopene-rich products and dietary photoprotection. Photochem Photobiol Sci 5:238–242. Scholar
  131. 131.
    Andreassi M, Andreassi L (2003) Antioxidants in dermocosmetology: from the laboratory to clinical application. J Cosmet Dermatol 2:153–160. Scholar
  132. 132.
    Chen P, Xu S, Qu J (2018) Lycopene protects keratinocytes against UVB radiation-induced carcinogenesis via negative regulation of FOXO3a through the mTORC2/AKT signaling pathway. J Cell Biochem 119:366–377. Scholar
  133. 133.
    Cooperstone JL, Tober KL, Riedl KM, Teegarden MD, Cichon MJ, Francis DM, Schwartz SJ, Oberyszyn TM (2017) Tomatoes protect against development of UV-induced keratinocyte carcinoma via metabolomic alterations. Sci Rep 7:5106. Scholar
  134. 134.
    Shen C, Wang S, Shan Y, Liu Z, Fan F, Tao L, Liu Y, Zhou L, Pei C, Wu H, Tian C, Ruan J, Chen W, Wang A, Zheng S, Lu Y (2014) Chemomodulatory efficacy of lycopene on antioxidant enzymes and carcinogen-induced cutaneum carcinoma in mice. Food Funct 5:1422–1431. Scholar
  135. 135.
    Yeh SL, Huang CS, Hu ML (2005) Lycopene enhances UVA-induced DNA damage and expression of heme oxygenase-1 in cultured mouse embryo fibroblasts. Eur J Nutr 44:365–370CrossRefGoogle Scholar
  136. 136.
    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. Scholar
  137. 137.
    Giovannucci E (1999) Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J Natl Cancer Inst 91:317–331CrossRefGoogle Scholar
  138. 138.
    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. Scholar
  139. 139.
    Lodi G, Franchini R, Warnakulasuriya S, Varoni EM, Sardella A, Kerr AR, Carrassi A, MacDonald LC, Worthington HV (2006) Interventions for treating oral leukoplakia. Cochrane Database Syst Rev 7:CD001829. Scholar
  140. 140.
    Ngoc NB, Lv P, Zhao WE (2018) Suppressive effects of lycopene and β-carotene on the viability of the human esophageal squamous carcinoma cell line EC109. Oncol Lett 15:6727–6732. Scholar
  141. 141.
    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 86:122–127CrossRefGoogle Scholar
  142. 142.
    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 29B:45–55CrossRefGoogle Scholar
  143. 143.
    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. Scholar
  144. 144.
    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. Scholar
  145. 145.
    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. Scholar
  146. 146.
    Capurso C, Vendemiale G (2017) The Mediterranean Diet Reduces the Risk and Mortality of the Prostate Cancer: A Narrative Review. Front Nutr 4:38. Scholar
  147. 147.
    Krinsky NI (1998) The antioxidant and biological properties of the carotenoids. Ann N Y Acad Sci 854:443–447CrossRefGoogle Scholar
  148. 148.
    Gong X, Marisiddaiah R, Zaripheh S, Wiener D, Rubin LP (2016) Mitochondrial β-carotene 9′,10′ oxygenase modulates prostate cancer growth via NF-κB inhibition: A lycopene-independent function. Mol Cancer Res 14:966–975. Scholar
  149. 149.
    Van Hoang D, Pham NM, Lee AH, Tran DN, Binns CW (2018) Dietary carotenoid intakes and prostate cancer risk: A case-control study from vietnam. Nutrients 10:E70. Scholar
  150. 150.
    Palozza P, Sestito R, Picci N, Lanza P, Monego G, Ranelletti FO (2008) The sensitivity to beta-carotene growth-inhibitory and proapoptotic effects is regulated by caveolin-1 expression in human colon and prostate cancer cells. Carcinogenesis 29:2153–2161. Scholar
  151. 151.
    Yang CM, Lu YL, Chen HY, Hu ML (2012) 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. Scholar
  152. 152.
    Stahl W, Sies H (2005) Bioactivity and protective effects of natural carotenoids. Biochim Biophys Acta 1740:101–107. Scholar
  153. 153.
    Rowles JL 3rd, Ranard KM, Smith JW, An R, Erdman JW Jr (2017) Increased dietary and circulating lycopene are associated with reduced prostate cancer risk: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis 20:361–377. Scholar
  154. 154.
    Lu QY, Hung JC, Heber D, Go VL, Reuter VE, Cordon-Cardo C, Scher HI, Marshall JR, Zhang ZF (2001) Inverse associations between plasma lycopene and other carotenoids and prostate cancer. Cancer Epidemiol Biomark Prev 10:749–756Google Scholar
  155. 155.
    Hwang ES, Bowen PE (2004) Cell cycle arrest and induction of apoptosis by lycopene in LNCaP human prostate cancer cells. J Med Food 7:284–289. Scholar
  156. 156.
    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. Scholar
  157. 157.
    Li D, Chen L, Zhao W, Hao J, An R (2016) MicroRNA-let-7f-1 is induced by lycopene and inhibits cell proliferation and triggers apoptosis in prostate cancer. Mol Med Rep 13:2708–2714CrossRefGoogle Scholar
  158. 158.
    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 59:1225–1230PubMedGoogle Scholar
  159. 159.
    Key TJ, Appleby PN, Travis RC, Albanes D, Alberg AJ, Barricarte A, Black A, Boeing H, Bueno-de-Mesquita HB, Chan JM, Chen C, Cook MB, Donovan JL, Galan P, Gilbert R, Giles GG, Giovannucci E, Goodman GE, Goodman PJ, Gunter MJ, Hamdy FC, Heliövaara M, Helzlsouer KJ, Henderson BE, Hercberg S, Hoffman-Bolton J, Hoover RN, Johansson M, Khaw KT, King IB, Knekt P, Kolonel LN, Le Marchand L, Männistö S, Martin RM, Meyer HE, Mondul AM, Moy KA, Neal DE, Neuhouser ML, Palli D, Platz EA, Pouchieu C, Rissanen H, Schenk JM, Severi G, Stampfer MJ, Tjønneland A, Touvier M, Trichopoulou A, Weinstein SJ, Ziegler RG, Zhou CK, Allen NE (2015) Endogenous Hormones Nutritional Biomarkers Prostate Cancer Collaborative Group. Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies. Am J Clin Nutr 102:1142–1157. Scholar
  160. 160.
    Morgia G, Voce S, Palmieri F, Gentile M, Lapicca G, Giannantoni A, Blefari F, Carini M, Vespasiani G, Santelli G, Arnone S, Pareo RM, Russo GI (2017) Association between selenium and lycopene supplementation and incidence of prostate cancer: Results from the post-hoc analysis of the procomb trial. Phytomedicine 34:1–5. Scholar
  161. 161.
    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 Biomark Prev 10:861–868Google Scholar
  162. 162.
    Gupta S (2007) Review prostate cancer chemoprevention current status and future prospect. Toxicol Appl Pharmacol 224:369–376. Scholar
  163. 163.
    Paur I, Lilleby W, Bøhn SK, Hulander E, Klein W, Vlatkovic L, Axcrona K, Bolstad N, Bjøro T, Laake P, Taskén KA, Svindland A, Eri LM, Brennhovd B, Carlsen MH, Fosså SD, Smeland SS, Karlsen AS, Blomhoff R (2016) Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA. Clin Nutr 36(3):672–679. Scholar
  164. 164.
    Wang Y, Jacobs EJ, Newton CC, McCullough ML (2016) Lycopene, tomato products and prostate cancer-specific mortality among men diagnosed with nonmetastatic prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Int J Cancer 138:2846–2855. Scholar
  165. 165.
    Yang CM, Yen YT, Huang CS, Hu ML (2011) Growth inhibitory efficacy of lycopene and β-carotene against androgen-independent prostate tumor cells xenografted in nude mice. Mol Nutr Food Res 55:606–612. Scholar
  166. 166.
    Soares ND, Machado CL, Trindade BB, Lima IC, Gimba ER, Teodoro AJ, Ch T, Borojevic R (2017) Lycopene extracts from different tomato-based food products induce apoptosis in cultured human primary prostate cancer cells and regulate TP53, Bax and Bcl-2 transcript expression. Asian Pac J Cancer Prev 18:339–345. Scholar
  167. 167.
  168. 168.
    Sharoni Y, Linnewiel-Hermoni K, Khanin M, Salman H, Veprik A, Danilenko M, Levy J (2012) Carotenoids and apocarotenoids in cellular signaling related to cancer: a review. Mol Nutr Food Res 56:259–269. Scholar
  169. 169.
    Ho WJ, Simon MS, Yildiz VO, Shikany JM, Kato I, Beebe-Dimmer JL, Cetnar JP, Bock CH (2015) Antioxidant micronutrients and the risk of renal cell carcinoma in the Women's Health Initiative cohort. Cancer 121:580–588. Scholar
  170. 170.
    Bock CH, Ruterbusch JJ, Holowatyj AN, Steck SE, Van Dyke AL, Ho WJ, Cote ML, Hofmann JN, Davis F, Graubard BI, Schwartz KL, Purdue MP (2018) Renal cell carcinoma risk associated with lower intake of micronutrients. Cancer Med 7(8):4087–4097. Scholar
  171. 171.
    Bertoia M, Albanes D, Mayne ST, Männistö S, Virtamo J, Wright ME (2010) No association between fruit, vegetables, antioxidant nutrients and risk of renal cell carcinoma. Int J Cancer 126:1504–1512. Scholar
  172. 172.
    Wang XD (2012) Lycopene metabolism and its biological significance. Am J Clin Nutr 96:1214S–1222S. Scholar
  173. 173.
    Sahin K, Cross B, Sahin N, Ciccone K, Suleiman S, Osunkoya AO, Master V, Harris W, Carthon B, Mohammad R, Bilir B, Wertz K, Moreno CS, Walker CL, Kucuk O (2015) Lycopene in the prevention of renal cell cancer in the TSC2 mutant Eker rat model. Arch Biochem Biophys 572:36–39. Scholar
  174. 174.
    Lee JE, Giovannucci E, Smith-Warner SA, Spiegelman D, Willett WC, Curhan GC (2006) Intakes of fruits, vegetables, vitamins A, C, and E, and carotenoids and risk of renal cell cancer. Cancer Epidemiol Biomark Prev 15:2445–2452. Scholar
  175. 175.
    Brock KE, Ke L, Gridley G, Chiu BC, Ershow AG, Lynch CF, Graubard BI, Cantor KP (2012) Fruit, vegetables, fibre and micronutrients and risk of US renal cell carcinoma. Br J Nutr 108:1077–1085. Scholar
  176. 176.
    Sahin K, Yenice E, Tuzcu M, Orhan C, Mizrak C, Ozercan IH, Sahin N, Yilmaz B, Bilir B, Ozpolat B, Kucuk O (2018) Lycopene protects against spontaneous ovarian cancer formation in laying hens. J Cancer Prev 23:25–36. Scholar
  177. 177.
    Holzapfel NP, Shokoohmand A, Wagner F, Landgraf M, Champ S, Holzapfel BM, Clements JA, Hutmacher DW, Loessner D (2017) Lycopene reduces ovarian tumor growth and intraperitoneal metastatic load. Am J Cancer Res 7:1322–1336PubMedPubMedCentralGoogle Scholar
  178. 178.
    Li X, Xu J (2014) Meta-analysis of the association between dietary lycopene intake and ovarian cancer risk in postmenopausal women. Sci Rep 4:4885. Scholar
  179. 179.
    Cramer DW, Kuper H, Harlow BL, Titus-Ernstoff L (2001) Carotenoids, antioxidants and ovarian cancer risk in pre- and postmenopausal women. Int J Cancer 94:128–134. Scholar
  180. 180.
    Kiani F, Knutsen S, Singh P, Ursin G, Fraser G (2006) Dietary risk factors for ovarian cancer: the Adventist Health Study (United States). Cancer Causes Control 17:137–146. Scholar
  181. 181.
    Helzlsouer KJ, Alberg AJ, Norkus EP, Morris JS, Hoffman SC, Comstock GW (1996) Prospective study of serum micronutrients and ovarian cancer. J Natl Cancer Inst 88:32–37. Scholar
  182. 182.
    Jeong NH, Song ES, Lee JM, Lee KB, Kim MK, Cheon JE, Lee JK, Son SK, Lee JP, Kim JH, Hur SY, Kwon YI (2009) Plasma carotenoids, retinol and tocopherol levels and the risk of ovarian cancer. Acta Obstet Gynecol Scand 88:457–462. Scholar
  183. 183.
    Zhang XF, Huang FH, Zhang GL, Bai DP, Massimo DF, Huang YF, Gurunathan S (2017) Novel biomolecule lycopene-reduced graphene oxide-silver nanoparticle enhances apoptotic potential of trichostatin A in human ovarian cancer cells (SKOV3). Int J Nanomedicine 12:7551–7575. Scholar
  184. 184.
    Jain A, Sharma G, Ghoshal G, Kesharwani P, Singh B, Shivhare US, Katare OP (2018) Lycopene loaded whey protein isolate nanoparticles: An innovative endeavor for enhanced bioavailability of lycopene and anti-cancer activity. Int J Pharm 546:97–105. Scholar
  185. 185.
    Uppala PT, Dissmore T, Lau BH, Andacht T, Rajaram S (2013) Selective Inhibition of cell proliferation by lycopene in MCF-7 breast cancer cells in vitro: a proteomic analysis. Phytother Res 27:595–601. Scholar
  186. 186.
    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. Scholar
  187. 187.
    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. Scholar
  188. 188.
    Seo JY, Masamune A, Shimosegawa T, Kim H (2009) Protective effect of lycopene on oxidativestress-induced cell death of pancreatic acinar cells. Ann N Y Acad Sci 1171:570–575. Scholar
  189. 189.
    Oguz E, Kocarslan S, Tabur S, Sezen H, Yilmaz Z, Aksoy N (2015) Effects of lycopene alone or combined with melatonin on methotrexate-induced nephrotoxicity in rats. Asian Pac J Cancer Prev 16:6061–6066CrossRefGoogle Scholar
  190. 190.
    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 87:1767–1776CrossRefGoogle Scholar
  191. 191.
    Tan HL, Thomas-Ahner JM, Moran NE, Cooperstone JL, Erdman JW Jr, Young GS, Clinton SK (2017) β-Carotene 9′,10′ oxygenase modulates the anticancer activity of dietary tomato or lycopene on prostate carcinogenesis in the TRAMP model. Cancer Prev Res (Phila) 10:161–169. Scholar
  192. 192.
    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. Scholar
  193. 193.
    Offord EA, Gautier JC, Avanti O, Scaletta C, Runge F, Krämer K, Applegate LA (2002) Photoprotective potential of lycopene, β-carotene, vitamin E, vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts. Free Radic Biol Med 32:1293–1303CrossRefGoogle Scholar
  194. 194.
    Chiang HS, Wu WB, Fang JY, Chen DF, Chen BH, Huang CC, Chen YT, Hung CF (2007) Lycopene inhibits PDGF-BB-induced signaling and migration in human dermal fibroblasts through interaction with PDGF-BB. Life Sci 81:1509–1517. Scholar
  195. 195.
    Butnariu M, Giuchici C (2011) The use of some nanoemulsions based on aqueous propolis and lycopene extract in the skin's protective mechanisms against UVA radiation. J Nanobiotechnol 9:3. Scholar
  196. 196.
    Ascenso A, Pinho S, Eleutério C, Praca FG, Bentley MV, Oliveira H, Santos C, Silva O, Simões S (2013) Lycopene from tomatoes: vesicular nanocarrier formulations for dermal delivery. J Agric Food Chem 61:7284–7293. Scholar
  197. 197.
    Kowalczyk MC, Walaszek Z, Kowalczyk P, Kinjo T, Hanausek M, Slaga TJ (2009) Differential effects of several phytochemicals and their derivatives on murine keratinocytes in vitro and in vivo: implications for skin cancer prevention. Carcinogenesis 30:1008–1015. Scholar

Copyright information

© Crown 2019

Authors and Affiliations

  • Kazim Sahin
    • 1
    Email author
  • Cemal Orhan
    • 1
  • Nurhan Sahin
    • 1
  • Omer Kucuk
    • 2
  1. 1.Department of Animal Nutrition, Faculty of Veterinary ScienceFirat UniversityElazigTurkey
  2. 2.Winship Cancer Institute of Emory UniversityAtlantaUSA

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