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Anticancer Properties of Lycopene

  • Living reference work entry
  • First Online:
Bioactive Molecules in Food

Part of the book series: Reference Series in Phytochemistry ((RSP))

  • 307 Accesses

Abstract

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.

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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

AOM:

Azoxymethane

ARE:

Antioxidant response element

BRCA:

Breast cancer

CAT:

Catalase

CDK:

Cyclin-dependent kinases

CI:

Confidence interval

COX-2:

Cyclooxygenase-2

Cx43:

Connexin 43

DEN:

Diethylnitrosamine

DMBA:

7,12-Dimethyl-benz[a]anthracene

DMH:

1,2-Dimethylhydrazine

ERK1:

Extracellular signal-regulated kinase 1

GJC:

Gap-junctional intercellular communication

GSK-3β:

Glycogen synthase kinase-3β

HCC:

Hepatocellular carcinoma

HepG2:

Human hepatocellular liver carcinoma cell line

HFD:

High-fat diet

IGF-1:

Insulin-like growth factor

IGFBP-3:

Insulin like growth factor binding protein 3

iNOS:

Inducible nitric oxide synthase

Keap-1:

Kelch-like ECH-associated protein 1-

LXRα:

Liver X receptor alpha

MCF-7:

Human breast adenocarcinoma cell line

MMP-2:

Matrix metalloproteinase 2

MMP-7:

Matrix metalloproteinase 7

MMP-9:

Matrix metalloproteinase 9

MNU:

N-methyl-N-nitrosourea

NADPH:

Nicotinamide adenine dinucleotide phosphate

NF-kB:

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

NNK:

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

Nrf2:

Nuclear factor-E2-related factor 2

ORs:

Odds ratios

PCB:

Polychlorinated biphenyls

PCNA:

Proliferating cellular nuclear antigen

p-mTOR:

Phosphorylated mammalian target of rapamycin

PPARγ:

Peroxisome proliferator-activated receptor gamma

PSA:

Prostate-specific antigen

RCC:

Renal cell carcinoma

ROS:

Reduction oxidative stress

SOD:

Superoxide dismutase

TNF-α:

Tumor necrosis factor-alpha

References

  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, 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

    Article  PubMed  Google Scholar 

  4. Tanaka T, Shinimizu M, Moriwaki H (2012) Cancer chemoprevention by carotenoids. Molecules 17:3202–3242. https://doi.org/10.3390/molecules17033202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.2174/156800912801784866

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1080/01635581.2014.894092

    Article  CAS  PubMed  Google Scholar 

  7. Nguyen ML, Schwartz SJ (1999) Lycopene: Chemical and biological properties. Food Technol 53:38–45

    CAS  Google Scholar 

  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. https://doi.org/10.4103/2008-7802.162311

    Article  PubMed Central  PubMed  Google Scholar 

  9. Ascenso A, Ribeiro H, Marques HC, Oliveira H, Santos C, Simões S (2014) Chemoprevention of photocarcinogenesis by lycopene. Exp Dermatol 23:874–878. https://doi.org/10.1111/exd.12491

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. van Breemen RB, Pajkovic N (2008) Multitargeted therapy of cancer by lycopene. Cancer Lett 269:339–351. https://doi.org/10.1016/j.canlet.2008.05.016

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Di Mascio P, Kaiser S, Sies H (1989) Lycopene as the most effective biological carotenoid singlet oxygen quencher. Arch Biochem Biophys 274:532–538

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1111/j.1600-0714.2010.00991.x

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  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 59:459–565

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1080/10408398.2011.623799

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.3390/molecules15020959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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) 227:886–893

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1093/jn/130.2.189

    Article  CAS  PubMed  Google Scholar 

  20. Agarwal S, Rao AV (1998) Tomato lycopene and low density lipoprotein oxidation: a human dietary intervention study. Lipids 33:981–984

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.3382/ps/pew012

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.jnutbio.2017.05.010

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.ejmech.2015.04.040

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.fct.2010.06.038

    Article  CAS  PubMed  Google Scholar 

  25. Mein JR, Lian F, Wang XD (2008) Biological activity of lycopene metabolites: implications for cancer prevention. Nutr Rev 66:667–683. https://doi.org/10.1111/j.1753-4887.2008.00120.x

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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 52:5707–5712

    CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1093/carcin/10.9.1743

    Article  CAS  PubMed  Google Scholar 

  29. 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 

  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 88:2825–2829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1002/(SICI)1097-0215(19981109)78:4<446::AID-IJC10>3.0.CO;2-4

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1006/abbi.1999.1510

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1093/jn/132.12.3754

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.abb.2008.10.022

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1002/mnfr.200700272

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1007/s13277-016-4798-3

    Article  Google Scholar 

  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. https://doi.org/10.1155/2013/705121

    Article  PubMed Central  PubMed  Google Scholar 

  38. Kelkel M, Schumacher M, Dicato M, Diederich M (2011) Antioxidant and anti-proliferative properties of lycopene. Free Radic Res 45:925–940. https://doi.org/10.3109/10715762.2011.564168

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1007/s00394-006-0595-x

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1097/01.cej.0000236251.09232.7b

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1096/fj.03-1116fje

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1371/journal.pone.0019652

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1007/s00011-009-0077-8

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1021/jf202433f

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.bmc.2006.06.045

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1007/s10549-011-1723-8

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.4178/epih.e2016024

    Article  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.foodres.2017.10.045

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.ejca.2004.03.028

    Article  CAS  PubMed  Google Scholar 

  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 36:254–257

    CAS  PubMed  Google Scholar 

  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. https://doi.org/10.4238/gmr16029434

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1038/sj.onc.1204452

    Article  CAS  PubMed  Google Scholar 

  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 21:118–123

    CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1080/01635581.2011.606955

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1080/02652048.2017

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1093/jnci/djs461

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1158/1055-9965.EPI-04-0683

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1093/ajcn/76.4.883

    Article  CAS  PubMed  Google Scholar 

  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 11:451–457

    CAS  Google Scholar 

  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. https://doi.org/10.1093/ajcn/66.3.626

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.nut.2010.12.019

    Article  CAS  PubMed  Google Scholar 

  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 13:40–48

    Article  Google Scholar 

  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. https://doi.org/10.1080/01635581.2015.1055365

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.3390/cancers3022333

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1093/carcin/bgm076

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1002/ijc.23696

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1093/ajcn/72.4.990

    Article  CAS  PubMed  Google Scholar 

  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 156:536–547

    Article  PubMed  Google Scholar 

  69. Graham DL, Carail M, Caris-Veyrat C, Lowe GM (2010) Cigarette smoke and human plasma lycopene depletion. Food Chem Toxicol 48:2413–2420. https://doi.org/10.1016/j.fct.2010.06.001

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.3389/fonc.2017.00023

    Article  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1080/01635589809514734

    Article  CAS  PubMed  Google Scholar 

  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 94:57–63

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1093/aje/kwn409

    Article  PubMed Central  PubMed  Google Scholar 

  74. Liu C, Russell RM (2008) Nutrition and gastric cancer risk: an update. Nutr Rev 66:237–249. https://doi.org/10.1111/j.1753-4887.2008.00029.x

    Article  PubMed  Google Scholar 

  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):1772–1780

    Google Scholar 

  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. https://doi.org/10.1016/S0271-5317(01)00321-9

    Article  Google Scholar 

  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 14:387–293

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.21010/ajtcam.v13i4.24

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1158/1055-9965.EPI-05-0038

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1207/s15327914nc5301_1

    Article  PubMed  Google Scholar 

  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 9:329–334

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1093/carcin/bgn072

    Article  CAS  Google Scholar 

  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 59:181–184

    Article  CAS  PubMed  Google Scholar 

  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 13:1772–1780

    CAS  Google Scholar 

  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. https://doi.org/10.1016/j.clnu.2015.02.003

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.3390/ijms12053340

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.2174/1871520618666180604085612

  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. https://doi.org/10.1002/mnfr.200900482

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  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. https://doi.org/10.1186/s12876-016-0432-5

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1177/153537020623100313

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1093/jn/138.3.538

    Article  PubMed  Google Scholar 

  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 4:177–186

    CAS  PubMed  Google Scholar 

  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 19:403–411

    Article  Google Scholar 

  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. https://doi.org/10.1515/BC.2006.012

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1021/acs.jafc.7b03036

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1080/01635589709514603

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1002/ijc.24689

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.jnutbio.2018.01.003

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1002/ijc.30161

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1158/1940-6207.CAPR-14-0154

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1080/01635581.2015.1087040

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1002/ijc.29175

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1159/000323933

    Article  PubMed  Google Scholar 

  105. Donaldson MS (2004) Nutrition and cancer: a review of the evidence for an anti-cancer diet. Nutr J 3:19. https://doi.org/10.1186/1475-2891-3-19

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  106. McCullough ML, Giovannucci EL (2004) Diet and cancer prevention. Oncogene 23:6349–6364. https://doi.org/10.1038/sj.onc.1207716

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1093/jn/135.3.592

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1038/srep38936

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1371/journal.pone.0137427

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1093/ajcn/49.5.895

    Article  CAS  PubMed  Google Scholar 

  111. Kim MJ, Kim H (2015) Anticancer effect of lycopene in gastric carcinogenesis. J Cancer Prev 20:92–96. https://doi.org/10.15430/JCP.2015.20.2.92

    Article  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1080/01635581.2016.1206579

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1186/1475-2867-12-36

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.2147/IJN.S79107

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1002/mnfr.20120013

    Article  CAS  PubMed  Google Scholar 

  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 59:9011–9021

    Article  CAS  PubMed  Google Scholar 

  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 120:15–22

    Article  CAS  PubMed  Google Scholar 

  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 89:1003–1008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Erhardt JG, Meisner C, Bode JC (2003) Lycopene, beta-carotene, and colorectal adenomas. Am J Clin Nutr 78:1219–1224. https://doi.org/10.1093/ajcn/78.6.1219

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1038/sj.ejcn.1601366

    Article  CAS  PubMed  Google Scholar 

  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 20:362–367

    Article  CAS  PubMed  Google Scholar 

  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 131:612–624

    Article  CAS  PubMed  Google Scholar 

  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 72:56–61

    Article  CAS  PubMed  Google Scholar 

  124. Stahl W, Sies H (2012) Photoprotection by dietary carotenoids: concept, mechanisms, evidence and future development. Mol Nutr Food Res 56:287–295. https://doi.org/10.1002/mnfr.201100232

    Article  CAS  PubMed  Google Scholar 

  125. Stahl W, Sies H (2007) Carotenoids and flavonoids contribute to nutritional protection against skin damage from sunlight. Mol Biotechnol 37:26–30

    Article  CAS  PubMed  Google Scholar 

  126. Wright TI, Spencer JM, Flowers FP (2006) Chemoprevention of nonmelanoma skin cancer. J Am Acad Dermatol 54:933–946. https://doi.org/10.1016/j.jaad.2005.08.062

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1155/2016/8214631

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1093/jn/125.7.1854

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1093/jn/131.5.1449

    Article  CAS  PubMed  Google Scholar 

  130. Stahl W, Heinrich U, Aust O, Tronnier H, Sies H (2006) Lycopene-rich products and dietary photoprotection. Photochem Photobiol Sci 5:238–242. https://doi.org/10.1039/b505312a

    Article  CAS  PubMed  Google Scholar 

  131. Andreassi M, Andreassi L (2003) Antioxidants in dermocosmetology: from the laboratory to clinical application. J Cosmet Dermatol 2:153–160. https://doi.org/10.1111/j.1473-2130.2004.00075.x

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1002/jcb.26189

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1038/s41598-017-05568-7

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1039/c4fo00035h

    Article  CAS  PubMed  Google Scholar 

  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 44:365–370

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.tiv.2008.03.001

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1080/07315724.2004.10719340

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1002/14651858.CD001829

    Article  Google Scholar 

  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. https://doi.org/10.3892/ol.2018.8175

    Article  PubMed Central  PubMed  Google Scholar 

  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 86:122–127

    Article  CAS  PubMed  Google Scholar 

  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:45–55

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/S0367-326X(01)00321-5

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.archoralbio.2010.12.007

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/S1368-8375(99)00050-0

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.3389/fnut.2017.00038

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  147. Krinsky NI (1998) The antioxidant and biological properties of the carotenoids. Ann N Y Acad Sci 854:443–447

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1158/1541-7786.MCR-16-0075

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.3390/nu10010070

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1093/carcin/bgn018

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.jnutbio.2011.06.009

    Article  CAS  PubMed  Google Scholar 

  152. Stahl W, Sies H (2005) Bioactivity and protective effects of natural carotenoids. Biochim Biophys Acta 1740:101–107. https://doi.org/10.1016/j.bbadis.2004.12.006

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1038/pcan.2017.25

    Article  CAS  PubMed  Google Scholar 

  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 10:749–756

    CAS  Google Scholar 

  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. https://doi.org/10.1089/jmf.2004.7.284

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1080/01635581.2011.523494

    Article  CAS  PubMed  Google Scholar 

  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 13:2708–2714

    Article  CAS  PubMed  Google Scholar 

  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 59:1225–1230

    CAS  PubMed  Google Scholar 

  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. https://doi.org/10.3945/ajcn.115.114306

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.phymed.2017.06.008

    Article  CAS  PubMed  Google Scholar 

  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 10:861–868

    CAS  Google Scholar 

  162. Gupta S (2007) Review prostate cancer chemoprevention current status and future prospect. Toxicol Appl Pharmacol 224:369–376. https://doi.org/10.1016/j.taap.2006.11.008

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.clnu.2016.06.01

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1002/ijc.30027

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1002/mnfr.201000308

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.22034/APJCP.2017.18.2.33

    Article  PubMed Central  PubMed  Google Scholar 

  167. https://www.cancer.org/cancer/kidney-cancer/about/key-statistics.html

  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. https://doi.org/10.1002/mnfr.201100311

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1002/cncr.29091

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1002/cam4.1639

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1002/ijc.24829

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  172. Wang XD (2012) Lycopene metabolism and its biological significance. Am J Clin Nutr 96:1214S–1222S. https://doi.org/10.3945/ajcn.111.032359

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.abb.2015.01.006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1158/1055-9965.EPI-06-0553

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1017/S0007114511006489

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.15430/JCP.2018.23.1.25

    Article  PubMed Central  PubMed  Google Scholar 

  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 7:1322–1336

    PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1038/srep04885

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1002/ijc.1435

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1007/s10552-005-5383-z

    Article  PubMed  Google Scholar 

  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. https://doi.org/10.1093/jnci/88.1.32

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1080/00016340902807215

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.2147/IJN.S144161

    Article  PubMed Central  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.ijpharm.2018.04.061

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1002/ptr.4764

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1177/0748233711416948

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1080/01635581.2012.643273

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1111/j.1749-6632.2009.04712.x

    Article  CAS  PubMed  Google Scholar 

  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 16:6061–6066

    Article  PubMed  Google Scholar 

  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 87:1767–1776

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1158/1940-6207.CAPR-15-0402

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1016/j.jnutbio.2010.10.006

    Article  CAS  PubMed  Google Scholar 

  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 32:1293–1303

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1016/j.lfs.2007.09.018

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1186/1477-3155-9-3

    Article  CAS  Google Scholar 

  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. https://doi.org/10.1021/jf401368w

    Article  CAS  PubMed  Google Scholar 

  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. https://doi.org/10.1093/carcin/bgp069

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig, Turkey

    Kazim Sahin, Cemal Orhan & Nurhan Sahin

  2. Winship Cancer Institute of Emory University, Atlanta, Georgia, USA

    Omer Kucuk

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  1. Kazim Sahin
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  2. Cemal Orhan
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  3. Nurhan Sahin
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  4. Omer Kucuk
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Correspondence to Kazim Sahin .

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  1. Gr. d'Etude Subst. Vég. à Act. Biol, Institut des Sciences de la Vigne e Gr. d'Etude Subst. Vég. à Act. Biol, Villenave d'Ornon, France

    Jean-Michel Mérillon

  2. M.L. Sukhadia University , Badgaon, Rajasthan, India

    K.G. Ramawat

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Sahin, K., Orhan, C., Sahin, N., Kucuk, O. (2018). Anticancer Properties of Lycopene. In: Mérillon, JM., Ramawat, K. (eds) Bioactive Molecules in Food. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-54528-8_88-1

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