Tomato lycopene and lung cancer prevention: From experimental to human studies

Cancers

Volumn 3, Issue 2, 2011, Pages 2333-2357

  Palozza, Paola ^a   Simone, Rossella E ^a   Catalano, Assunta ^a   Mele, Maria Cristina ^a  

^a CATHOLIC UNIVERSITY   (Italy)

Author keywords

Apoptosis; Cancer cell proliferation; Carotenoids; Lung cancer prevention; Lycopene; Lycopene metabolites

Indexed keywords

BETA CAROTENE; CAROTENOID; CHOLESTEROL; CONNEXIN 43; CYCLIN D1; CYCLIN DEPENDENT KINASE INHIBITOR 1; CYCLINE; CYTOCHROME P450 1A1; CYTOCHROME P450 1A2; CYTOCHROME P450 2B1; CYTOCHROME P450 2B2; CYTOCHROME P450 2E1; CYTOCHROME P450 3A; CYTOKINE; GELATINASE A; GELATINASE B; GLUTATHIONE TRANSFERASE; LYCOPENE; PLANT EXTRACT; PROTEIN BAD; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BID; PROTEIN P53; SOMATOMEDIN BINDING PROTEIN 3; SOMATOMEDIN C; TOMATO EXTRACT; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; CANCER CELL CULTURE; CANCER INHIBITION; CANCER RESEARCH; CANCER RISK; CELL COMMUNICATION; CELL CYCLE ARREST; CELL GROWTH; CELL PROLIFERATION; CHEMICAL INTERACTION; CIGARETTE SMOKING; DIET SUPPLEMENTATION; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG LUNG LEVEL; DRUG MEGADOSE; DRUG TISSUE LEVEL; ENZYME INDUCTION; EXPERIMENTAL STUDY; FERRET; FOOD COMPOSITION; FOOD INTAKE; GAP JUNCTION; HUMAN; INHIBITION KINETICS; ISOMERIZATION; LIVER TOXICITY; LOW DRUG DOSE; LUNG ADENOMA; LUNG CANCER; LUNG METASTASIS; LUNG TOXICITY; METASTASIS INHIBITION; MOUSE; NEPHROTOXICITY; NONHUMAN; OXIDATION REDUCTION STATE; PNEUMONIA; RAT; RESEARCH SUBJECT; REVIEW; SIGNAL TRANSDUCTION; TOMATO; TRANSCRIPTION REGULATION;

EID: 79959724646     PISSN: None     EISSN: 20726694     Source Type: Journal    
DOI: 10.3390/cancers3022333     Document Type: Review

References (158)

1. Pryor, W.A. Mechanisms of radical formation from reactions of ozone with target molecules in the lung. Free Radic. Biol. Med. 1994, 17, 451-465.
2. Cross, C.E.; van der Vliet, A.; O'Neill, C.A.; Louie, S.; Halliwell, B. Oxidants, antioxidants, and respiratory tract lining fluids. Environ. Health Perspect. 1994, 102, 185-191.
3. Schwartz, J.; Weiss, S.T. Relationship between dietary vitamin C intake and pulmonary function in the First National Health and Nutrition Examination Survey (NHANES I). Am. J. Clin. Nutr. 1994, 59, 110-114.
4. Schmitz, H.H.; Poor, C.L.; Wellman, R.B.; Erdman, J.W. Concentrations of selected carotenoids and vitamin A in human liver, kidney and lung tissue. J. Nutr. 1991, 121, 1613-1621.
5. Redlich, C.A.; Blaner, W.S.; Van Bennekum, A.M.; Chung, J.S.; Clever, S.L.; Holm, C.T.; Cullen, M.R. Effect of supplementation with β-carotene and vitamin A on lung nutrient levels. Cancer Epidemiol. Biomarkers Prev. 1998, 7, 211-214.
6. Hilbert, J.; Mohensin, V. Adaptation of lung antioxidants to cigarette smoking in humans. Chest 1996, 110, 916-920.
7. Redlich, C.A.; Grauer, J.N.; Van Bennekum, A.M.; Clever, S.L.; Ponn, R.B.; Blaner, W.S. Characterization of carotenoid, vitamin A, and β-tocopherol levels in human lung tissue and pulmonary macrophages. Am. J. Respir. Crit. Care Med. 1996, 154, 1436-1443.
8. Omenn, G.S.; Goodman, G.E.; Thornquist, M.D. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J. Natl. Cancer Inst. 1996, 88, 1550-1559.
9. Virtamo, J.; Pietinen, P.; Huttunen, J.K.; Korhonen, P.; Malila, N.; Virtanen, M.J.; Albanes, D.; Taylor, P.R.; Albert, P.; ATBC Study Group. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: A postintervention follow-up. JAMA 2003, 290, 476-485.
10. Straub, O. Lists of natural carotenoids. In Key to Carotenoids; Pfander, H., Basel, H., Eds.; Verlag: Birkhauser, Switzerland, 1987.
11. Clinton, S.K. Lycopene: Chemistry, biology, and implications for human health and disease. Nutr. Rev. 1998, 56, 35-51.
12. Tonucci, L.H.; Holden, J.M.; Beecher, G.; Khachik, F.; Davis, C.S.; Mulokozi, G. Carotenoid content of thermally processed tomato-based food products. J. Agric. Food Chem. 1995, 43, 579-586.
13. Bohm, V.; Frohlich, K.; Bitsch, R. Rosehip-A "new" source of lycopene. Mol. Aspects Med. 2003, 24, 385-389.
14. Mangels, A.R.; Holden, J.M.; Beecher, G.R.; Forman M.R.; Lanza, E. Carotenoid content of fruits and vegetables: An evaluation of analytic data. J. Am. Diet. Assoc. 1993, 93, 284-296.
15. Stahl, W.; Schwarz, W.; Sundquist, A.R.; Sies, H. Cis-trans isomers of lycopene and beta-carotene in human serum and tissues. Arch. Biochem. Biophys. 1992, 294, 173-177.
16. Rao, A.V.; Ray, M.R.; Rao, L.G. Lycopene. Adv. Food Nutr. Res. 2006, 51, 99-164.
17. Gärtner, C.; Stahl, W.; Sies, H. Lycopene is more bioavailable from tomato paste than from fresh tomatoes. Am. J. Clin. Nutr. 1997, 66, 116-122.
18. Zaripheh, S.; Erdman, Jr., J.W. The biodistribution of a single oral dose of [14C]-lycopene in rats prefed either a control or lycopene-rich diet. J. Nutr. 2005, 135, 2212-2218.
19. Liu, A.; Pajkovic, N.; Pang, Y.; Zhu, D.; Calamini, B.; Mesecar, A.L.; van Breemen, R.B. Absorption and subcellular localization of lycopene in human prostate cancer cells. Mol. Cancer Ther. 2006, 5, 2879-2885.
20. Khachik, F.; Carvallo, L.; Bernstein, P.S.; Muir, G.J.; Zhao, D.Y.; Katz, N.B. Chemistry, distribution and metabolism of tomato carotenoids and their impact on human health. Exp. Biol. Med. 2002, 227, 845-851.
21. Kopec, R.E.; Riedl, K.M.; Harrison, E.H.; Curley, R.W., Jr.; Hruszkewycz, D.P.; Clinton, S.K.; Schwartz, S.J. Identification and quantification of apo-lycopenals in fruits, vegetables, and human plasma. J. Agric. Food Chem. 2010, 58, 3290-3296.
22. Ben-Aziz, A.; Britton, G.; Goodwin, T.W. Carotene epoxides of lycopersicon esculentum, Phytochemistry 1973, 12, 2759-2764.
23. Khachik, F.; Spangler, C.J.; Smith, J.C., Jr.; Canfield, L.M.; Steck, A.; Pfander, H. Identification, quantification, and relative concentrations of carotenoids and their metabolites in human milk and serum. Anal. Chem. 1997, 69, 1873-1881.
24. Rao, A.V.; Agarwal, S. Role of antioxidant lycopene in cancer and heart disease. J. Am. Coll. Nutr. 2000, 19, 563-569.
25. Peters, U.; Leitzmann, M.F.; Chatterjee, N.; Wang, Y.; Albanes, D.; Gelmann, E.P.; Friesen, M.D.; Riboli, E.; Hayes, R.B. Serum lycopene, other carotenoids, and prostate cancer risk: A nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol. Biomarker. Prev. 2007, 5, 962-968.
26. Krinsky, N.I. The antioxidant and biological properties of the carotenoids. Ann. NY Acad. Sci. 1998, 854, 443-447.
27. Richard, B.; van Breemen, N.P. Multitargeted therapy of cancer by lycopene. Cancer Lett. 2008, 269, 339-351.
28. Zhang, L.X.; Cooney, R.V.; Bertram, J.S. Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/ 10T1/2 cells: Relationship to their cancer chemopreventive action. Carcinogenesis 1991, 12, 2109-2114.
29. Zhang, L.X.; Cooney, R.V.; Bertram, J.S. Carotenoids up-regulate connexin43 gene expression independent of their provitamin A or antioxidant properties. Cancer Res. 1992, 52, 5707-5712.
30. Levy, J.; Bosin, E.; Feldmen, B.; Giat, Y.; Miinster, A.; Danilenko, M.; Sharoni, Y. Lycopene is a more potent inhibitor of human cancer cell proliferation than either a-carotene or b-carotene. Nutr. Cancer 1995, 24, 257-266.
31. Nagasawa, H.; Mitamura, T.; Sakamoto, S.; Yamamoto, K. Effects of lycopene on spontaneous mammary tumour development in SHN virgin mice. Anticancer Res. 1995, 15, 1173-1178.
32. Kobayashi, T.; Iijima, K.; Mitamura, T.; Toriizuka, K.; Cyong, J.C.; Nagasawa, H. Effects of lycopene, a carotenoid, on intrathymic T cell differentian and peripheral CD4/CD8 ratio in a high mammary tumor strain of SHN retired mice. Anti-Cancer Drugs 1996, 7, 195-198.
33. Palozza, P.; Parrone, N.; Catalano, A.; Simone, R. Tomato lycopene and inflammatory cascade: Basic interactions and clinical implications. Curr. Med. Chem. 2010, 23, 2547-2563.
34. Astrog, P.; Gradelet, S.; Berges, R.; Suschetet, M. Dietary lycopene decreases initiation of liver preneoplastic foci by diethylnitrosamine in rat. Nutr. Cancer 1997, 29, 60-68.
35. Fuhramn, B.; Elis, A.; Aviram, M. Hypocholesterolemic effect of lycopene and b-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophage. Biochem. Biophys. Res. Commun. 1997, 233, 658-662.
36. Palozza, P.; Simone, R.; Catalano, A.; Parrone, N.; Monego, G.; Ranelletti, F.O. Lycopene regulation of cholesterol synthesis and efflux in human macrophages. J. Nutr. Biochem. 2011, in press.
37. Pincemail, J. Free Radicals and Antioxidants in Human Disease; Birkha user Verlag: Basel, Switzerland, 1995; pp. 83-98.
38. Ames, B.N.; Gold, L.S.; Willet, W.C. Causes and prevention of cancer. Proc. Natl. Acad. Sci. USA 1995, 92, 5258-5265.
39. Halliwell, B. Free radicals, antioxidants and human disease: Curiosity, cause or consequence? Lancet 1994, 344, 721-724.
40. Miller, N.J.; Sampson, J.; Candeias, L.P.; Bramley, P.M.; Rice-Evans, C.A. Antioxidant activities of carotenes and xanthophylls. FEBS Lett. 1996, 384, 240-246.
41. Rao, A.V.; Agarwal, S. Bioavailability and in vivo antioxidant properties of lycopene from tomato products and their possible role in the prevention of cancer. Nutr. Cancer 1998, 31, 199-203.
42. Pool-Zobel, B.L.; Bub, A.; Muller, H.; Wollowski, I.; Rechkemmer, G. Consumption of vegetables reduces genetic damage in humans: First result of a human intervention trial with carotenoid-rich foods. Carcinogenesis 1997, 18, 1847-1850.
43. Di Mascio, P.; Kaiser, S.; Sies, H. Lycopene as the most effective biological carotenoid singlet oxygen quencher. Arch. Biochem. Biophys. 1989, 274, 532-538.
44. Muzandu, K.; Ishizuka, M.; Sakamoto, K.Q.; Shaban, Z.; El Bohi, K.; Kazusaka, A.; Fujita, S. Effect of lycopene and betacarotene on peroxynitrite-mediated cellular modifications. Toxicol. Appl. Pharmacol. 2006, 215, 330-340.
45. Muzandu, K.; El Bohi, K.; Shaban, Z.; Ishizuka, M.; Kazusaka, A.; Fujika, S. Lycopene and beta-carotene ameliorate catechol estrogen-mediated DNA damage. J. Vet. Res. 2005, 52, 173-184.
46. Park, Y.O.; Hwang, E.S.; Moon, T.W. The effect of lycopene on cell growth and oxidative DNA damage of Hep3B human hepatoma cells. Biofactors 2005, 23, 129-139.
47. Chalabi, N.; Le Corre, L.; Mauizis, J.C.; Bignon, Y.J.; Bernard-Gallon, D. The effects of lycopene on the proliferation of human breast cells and BRCA1 and BRCA2 gene expression. Eur. J. Cancer 2004, 40, 1768-1775.
48. Fornelli, F.; Leone, A.; Verdesca, I.; Minervini, F.; Zacheo, G. The influence of lycopene on the proliferation of breast cell line (MCF-7). Toxicol. In Vitro 2007, 21, 217-223.
49. Hwang, E.S.; Bowen, P.E. Cell cycle arrest and induction of apoptosis by lycopene in LNCaP human prostate cells. J. Med. Food 2004, 7, 284-289.
50. Kim, L.; Rao, V.; Rao, L. Effects of Lycopene on prostate LNCaP cancer cells in culture. J. Med. Food 2002, 5, 181-187.
51. Livny, O.; Kaplan, I.; Reifen, R.; Polak-Charcon, S.; Madar, Z. Lycopene inhibits proliferation and enhances gap-junctional communication on KB-1 human oral tumor cells. J. Nutr. 2002, 132, 3754-3759.
52. Pastori, M.; Pfander, H.; Boscoboinik, D.; Azzi, A. Lycopene in association with α-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells. Biochem. Biophys. Res. Comm. 1998, 250, 582-585.
53. Reddy, M.K.; Alexander-Lindo, R.L.; Nair, M. G. Relative inhibition of lipid peroxidation, cyclooxygenase enzymes, and human tumor cell proliferation by natural food colors. J. Agric. Food Chem. 2005, 53, 9268-9273.
54. Salman, H.; Bergman, M.; Djaldetti, M.; Bessler, H. Lycopene affects proliferation and apoptosis of four malignant cell lines. Biomed. Pharm. 2007, 6, 366-375.
55. Tang, L.; Jin, T.; Zeng, X.; Wang, J.S. Lycopene inhibits the growth of human androgen-independent prostate cancer cells in vitro and in BALB/c nude mice. J. Nutr. 2005, 135, 287-290.
56. Palozza, P.; Colangelo, M.; Simone, R.; Catalano, A.; Boninsegna, A.; Lanza, P.; Monego, G.; Ranelletti, F.O. Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras signaling in cancer cell lines. Carcinogenesis 2010, 10, 1813-1821.
57. Hantz, H.L.; Young, L.F.; Martin, K.R. Physiologically attainable concentrations of lycopene induce mitochondrial apoptosis in LNCaP human prostate cancer cells. Exp. Biol. Med. 2005, 230, 171-179.
58. Lynn, C.; Burgess, E. R.; Fischer, T.; Seekins, R.J.; Tyler, P.; Burgess, S.; Sticka, J.; Kodi, K. 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 2008, 5, 1297-1300.
59. Huang, C.S.; Shih, M.K.; Chuang, C.H.; Hu, M.L. Lycopene inhibits cell migration and invasion and upregulates nm23-H1 in a highly invasive hepatocarcinogma, SK-Hep-1 cells. J. Nutr. 2005, 135, 2119-2123.
60. Hwang, E.S.; Lee, H.J. Inhibitory effects of lycopene on the adhesion, invasion, and migration of SK-Hep1 human hepatoma cells. Exp. Biol. Med. 2006, 231, 322-327.
61. Huang, C.S.; Fan, Y.E.; Lin, C.Y.; Hu, M.L. Lycopene inhibits matrix metalloproteinase-9 and down-regulates the binding activity of nuclear factor kappa B and stimulatory protein-1. J. Nutr. Biochem. 2007, 18, 449-456.
62. Boileau, T.W.M.; Clinton, S.K.; Erdman, J.W. Tissue lycopene concentrations and isomer patterns are affected by androgen status and dietary lycopene concentration in male F344 rats. J. Nutr. 2000, 130, 1613-1618.
63. Zhao, Z.; Khachik, F.; Richie, J.P.; Cohen, L.A. Lycopene uptake and tissue disposition in male and female rats. Proc. Soc. Exp. Biol. Med. 1998, 218, 109-114.
64. Liu, C.; Lian, F.; Smith, D.E.; Russell, R.M; Wang, X.D. Lycopene supplementation inhibits lung squamous metaplasia and induces apoptosis via up-regulating insulin-like growth factor-binding protein 3 in cigarette smoke-exposed ferrets. Cancer Res. 2003, 63, 3138-3144.
65. Liu, C.; Wang, X.D.; Bronson, R.T.; Smith, D.E.; Krinsky, N.I.; Russell, R.M. Effects of physiological versus pharmacological β-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets. Carcinogenesis 2000, 21, 2245-2253.
66. Liu, C.; Russell, R.M.; Wang, X.D. Exposing ferrets to cigarette smoke and a pharmacological dose of -carotene supplementation enhance in vitro retinoic acid catabolism in lungs via induction of cytochrome P450 enzymes. J. Nutr. 2003, 133, 173-179.
67. Liu, C.; Russell, R.M.; Seitz, H.K.; Wang, X.D. Ethanol enhances retinoic acid metabolism into polar metabolites in rat liver via induction of cytochrome P4502E1. Gastroenterology 2001, 120, 179-189.
68. Wang, X.D.; Liu, C.; Bronson, R.T.; Smith, D.E.; Krinsky, N.I.; Russell, M. Retinoid signaling and activator protein-1 expression in ferrets given β-carotene supplements and exposed to tobacco smoke. J. Natl. Cancer Inst. 1999, 91, 60-66.
69. Kim, D.J.; Takasuka, N.; Kim, J.M.; Sekine, K.; Ota, T.; Asamoto, M.; Murakoshi, M.; Nishino, H.; Nir, Z.; Tsuda, H. Chemoprevention by lycopene of mouse lung neoplasia after combined initiation treatment with DEN, MNU and DMH. Cancer Lett. 1997, 120, 15-22.
70. Hecht, S.S.; Kenney, P.M.; Wang, M.; Trushin, M.; Agarwal, S.; Rao, A.V.; Upadhyaya, P. Evaluation of butylated hydroxyanisole, myoinositol, curcumin, esculetin, resveratrol and lycopene as inhibitors of benzo[a]pyrene plus 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice. Cancer Lett. 1999, 137, 123-130.
71. Guttenplan, J.B.; Chen, M.; Kosinska, W.; Thompson, S.; Zhao, Z.; Cohen, L.A. Effects of a lycopene-rich diet on spontaneous and benzo[a]pyrene-induced mutagenesis in prostate, colon and lungs of the lacZ mouse. Cancer Lett. 2001, 1, 1-6.
72. Jamshidzadeh, A.; Baghban, M.; Azarpira, N.; Bardbori, A.M.; Niknahad, H. Effects of tomato extract on oxidative stress induced toxicity in different organs of rats. Food Chem. Toxicol. 2008, 46, 3612-3615.
73. Huang, C.S.; Liao, J.W.; Hu, M.L. Lycopene inhibits experimental metastasis of human hepatoma SK-Hep-1 cells in athymic nude mice. J. Nutr. 2008, 138, 538-543.
74. Böhm, F.; Tinkler, J.H.; Truscott, T.G. Carotenoids protect against cell membrane damage by the nitrogen dioxide radical. Nat. Med. 1995, 2, 98-99.
75. Lu, Y.; Etoh, H.; Watanaba, N. A new carotenoid, hydrogen peroxide oxidation products from lycopene. Biosci. Biotechnol. Biochem. 1995, 59, 2153-2155.
76. Mortensen, A.; Skibsted, L.H.; Sampson, J.; Rice-Evans, C.; Everett, S.A. Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants. FEBS Lett. 1997, 418, 91-97.
77. Devasagayam, T.P.; Werner, T.; Ippendorf, H.; Martin, H.D.; Sies, H. Synthetic carotenoids, novel polyene polyketones and new capsorubin isomers as efficient quenchers of singlet molecular oxygen. Photochem. Photobiol. 1992, 55, 511-514.
78. Miller, N.J.; Sampson, J.; Candeias, L.P.; Bramley, P.M.; Rice-Evans, C.A. Antioxidant activities of carotenes and xanthophylls. FEBS Lett. 1996, 384, 240-242.
79. Woodall, A.A.; Britton, G.; Jackson, M.J. Carotenoids and protection of phospholipids in solution or in liposomes against oxidation by peroxyl radicals: Relationship between carotenoid structure and protective ability. Biochim. Biophys. Acta 1997, 1336, 575-586.
80. Lowe, G.M.; Bilton, R.F.; Davies, I.G.; Ford, T.C.; Billington, D.; Young, A.J. Carotenoid composition and antioxidant potential in subfractions of human low-density lipoprotein. Ann. Clin. Biochem. 1999, 36, 323-332.
81. Yeh, S.; Hu, M. Antioxidant and pro-oxidant effects of lycopene in comparison with beta-carotene on oxidant-induced damage in Hs68 cells. J. Nutr. Biochem. 2000, 11, 548-554.
82. Stahl, W.; Junghans, A.; deBoer, B.; Driomina, E.S.; Briviba, K.; Sies, H. Carotenoid mixtures protect multilamellar liposomes against oxidative damage: Synergistic effects of lycopene and lutein. FEBS Lett. 1998, 427, 305-308.
83. Palozza, P.; Parrone N.; Simone, R.; Catalano, A. Role of lycopene in the control of ROS-mediated cell growth. Implications in cancer prevention. Curr. Med. Chem. 2011, in press.
84. Erdman, J.W., Jr.; Ford, N.A.; Lindshield, B.L. Are the health attributes of lycopene related to its antioxidant function Arch. Biochem. Biophys. 2009, 483, 229-235.
85. Nahum, A.; Hirsch, K.; Danilenko, M. 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 2001, 26, 3428-3436.
86. Palozza, P.; Serini, S.; Di Nicuolo, F.; Calviello, G. Modulation of apoptotic signalling by carotenoids in cancer cells. Arch. Biochem. Biophys. 2004, 1, 104-109.
87. Seo, Y.; Masamune, A.; Shimosegawa, T.; Kim, H. Protective effect of lycopene on oxidative stress-induced cell death of pancreatic acinar cells jeong. Ann. NY Acad. Sci. 2009, 1171, 570-575.
88. Siler, U.; Barella, L.; Spitzer, V.; Schnorr, J.; Lein, M.; Goralczyk, R.; Wertz, K. Lycopene and vitamin E interfere with autocrine/paracrine loops in the Dunning prostate cancer model. FASEB J. 2004, 19, 1019-1021.
89. Herzog, A.; Siler, U.; Spitzer, V.; Seifert, N.; Denelavas, A.; Hunziker, P.B.; Hunziker, W.; Goralczyk, R.; Wertz, K. Lycopene reduced gene expression of steroid targets and inflammatory markers in normal rat prostate. FASEB J. 2005, 2, 272-274.
90. Walfisch, S.; Walfisch, Y.; Kirilov, E.; Linde, N.; Mnitentag, H.; Agbaria, R.; Sharoni, Y.; Levy, J. Tomato lycopene extract supplementation decreases insulin-like growth factor-I levels in colon cancer patients. Eur. J. Cancer Prev. 2007, 4, 298-303.
91. Riso, P.; Brusamolino, A.; Martinetti, A.; Porrini, M. Effect of a tomato drink intervention on insulin-like growth factor (IGF)-1 serum levels in healthy subjects. Nutr. Cancer 2006, 2, 157-162.
92. Vrieling, A.; Voskuil, D.W.; Bonfrer, J.M.; Korse, C.M.; van Doorn, J.; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.; van Leeuwen, F.E.; et al. Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer. Am. J. Clin. Nutr. 2007, 5, 1456-1462.
93. Karas, M.; Amir, H.; Fishman, D.; Danilenko, M.; Segal, S.; Nahun, A.; Koifman, A.; Giat, Y.; Levy, J.; Sharoni, Y. Lycopene interferes with cell cycle progression and insuline-growth factor I signalling in mammary cancer cells. Nutr. Cancer 2000, 1, 101-111.
94. Karas, M.; Danilenko, M.; Fishman, D.; LeRoith, D.; Levy, J.; Sharoni, Y. Membrane-associated insulin-like growth factorbinding protein-3 inhibits insulin-like growth factor-Iinduced insulin-like growth factor-I receptor signaling in ishikawa endometrial cancer cells. J. Biol. Chem. 1997, 26, 16514-16520.
95. Nahum, A.; Zeller, L.; Danilenko, M.; Prall, O.W.; Watts, C.K.; Sutherland, R.L.; Levy, J.; Sharoni, Y. Lycopene inhibition of IGF-induced cancer cell growth depends on the level of cyclin D1. Eur. J. Nutr. 2006, 5, 275-282.
96. Wang, X.D. Carotenoids and Retinoids, Molecular Aspects and Health Issues; Packer, L., Kraemer, K., Obermuller-Jevic, U., Sies, H., Eds.; AOCS Press: Champaign, IL, USA, 2004; Volume 32, pp. 168-181.
97. Palozza, P.; Sheriff, A.; Serini, S.; Boninsegna, A.; Maggiano, N.; Ranelletti, F.O.; Calviello, G.; Cittadini, A. Lycopene induces apoptosis in immortalized fibroblasts exposed to tobacco smoke condensate through arresting cell cycle and down-regulating cyclin D1 pAKT and pBad. Apoptosis 2005, 6, 1445-1456.
98. Bhuvaneswari, V.; Velmurugan, B.; Balasenthil, S.; Ramachandran, C.R.; Nagini, S. Chemopreventive efficacy of lycopene on 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Fitoterapia 2001, 8, 865-874.
99. Astorg, P.; Gradelet, S.; Berges, R.; Suschetet, M. Dietary lycopene decreases the initiation of liver preneoplastic foci by diethylnitrosamine in the rat. Nutr. Cancer 1997, 1, 60-68.
100. Breinholt, V.; Lauridsen, S.T.; Daneshvar, B.; Jakobsen, J. Dose-response effects of lycopene on selected drug-metabolizing and antioxidant enzymes in the rat. Cancer Lett. 2000, 2, 201-210.
101. Aung, H.H.; Vasu, V.T.; Valacchi, G.; Corbacho, A.M.; Kota, R.S.; Lim, Y.; Obermueller-Jevic, U.C.; Packer, L.; Cross, C.E.; Gohil, K. Effects of dietary carotenoids on mouse lung genomic profiles and their modulatory effects on short-term cigarette smoke exposures. Genes Nutr. 2009, 1, 23-39.
102. Aust, O.; Ale-Agha, N.; Zhang, L.; Wollersen, H.; Sies, H.; Stahl, W. Lycopene oxidation product enhances gap junctional communication. Food Chem. Toxicol. 2003, 10, 1399-1407.
103. Sharoni, Y.; Danilenko, M.; Dubi, N.; Ben-Dor, A.; Levy, J. Carotenoids and transcription. Arch. Biochem. Biophys. 2004, 1, 89-96.
104. Stahl, W.; von Laar, J.; Martin, H.D.; Emmerich, T.; Sies, H. Stimulation of gap junctional communication: Comparison of acyclo- retinoic acid and lycopene. Arch. Biochem. Biophys. 2000, 1, 271-274.
105. Elson, C.E.; Peffley, D.M.; Hentosh, P.; Mo, H. Isoprenoid-mediated inhibition of mevalonate synthesis: potential application to cancer. Proc. Soc. Exp. Biol. Med. 1999, 22, 294-310.
106. Jackson, S.M.; Ericsson, J; and Edwards, P.A. Signaling molecules derived from the cholesterol biosynthetic pathway. Subcell. Biochem. 1997, 28, 1-21.
107. Heldin, C.H.; Westermark, B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol. Rev 1999, 79, 1283-1316.
108. Ruiter, D.; Bogenrieder, T.; Elder, D.; Herlyn, M. Melanoma-stroma interactions: Structural and functional aspects. Lancet Oncol. 2002, 3, 35-43.
109. Chiang, H.S.; Wu, W.B.; Fang, J.Y.; Chen, D.F.; Chen, B.H.; Huang, C.C.; Chen, Y.T.; Hung, C. F. Lycopene inhibits PDGF-BB-induced signalling and migration in human dermal fibroblasts through interaction with PDF-BB. Life Sci. 2007, 81, 1509-1517.
110. Kim, S.J.; Nara, E.; Kobayashi, H.; Terao, J.; Nagao, A. Formation of cleavage products by autoxidation of lycopene. Lipids 2001, 36, 191-199.
111. Caris-Veyrat, C.; Schmid, A.; Carail, M.; Bohm, V. Cleavage products of lycopene produced by in vitro oxidations: Characterization and mechanisms of formation. J. Agric. Food Chem. 2003, 51, 7318-7325.
112. Zhang, H.; Kotake-Nara, E.; Ono, H.; Nagao, A. A novel cleavage product formed by autoxidation of lycopene induces apoptosis in HL-60 cells. Free Radic. Biol. Med. 2003, 35, 1653-1663.
113. dos Anjos Ferreira, A.L.; Yeum, K.J.; Russell, R.M.; Krinsky, N.I.; Tang, G. Enzymatic and oxidative metabolites of lycopene. J. Nutr. Biochem. 2004, 15, 493-502.
114. Gajic, M.; Zaripheh, S.; Sun, F.; Erdman, J.W., Jr. Apo-80-lycopenal and apo-120-lycopenal are metabolic products of lycopene in rat liver. J. Nutr. 2006, 136, 1552-1557.
115. Hu, K.Q.; Liu, C.; Ernst, H.; Krinsky, N.I.; Russell, R.M.; Wang, X.D. The biochemical characterization of ferret carotene-90,100-monooxygenase catalyzing cleavage of carotenoids in vitro and in vivo. J. Biol. Chem. 2006, 281, 19327-19338.
116. Ben-Dor, A.; Steiner, M.; Gheber, L.; Danilenko, M.; Dubi, N.; Linnewiel, K.; Zick, A.; Sharoni, Y.; Levy, J. Carotenoids activate the antioxidant response element transcription system. Mol. Cancer Ther. 2005, 4, 177-186.
117. Linnewiel, K.; Ernst, H.; Caris-Veyrat, C.; Ben-Dor, A.; Kampf, A.; Salman, H.; Danilenko, M.; Levy, J.; Sharoni, Y. Structure activity relationship of carotenoid derivatives in activation of the electrophile/antioxidant response element transcription system. Free Radic. Biol. Med. 2009, 47, 659-667.
118. Lian, F.; Smith, D.E.; Ernst, H.; Russell, R.M.; Wang, X.D. Apo-100-lycopenoic acid inhibits lung cancer cell growth in vitro, and suppresses lung tumorigenesis in the A/J mouse model in vivo. Carcinogenesis 2007, 28, 1567-1574.
119. Lian, F.; Wang, X.D. Enzymatic metabolites of lycopene induce Nrf2-mediated expression of phase II detoxifying/antioxidant enzymes in human bronchial epithelial cells. Int. J. Cancer 2008, 123, 1262-1268.
120. De Stefani, E.; Brennan, P.; Boffetta, P.; Mendilaharsu, M.; Deneo-Pellegrini, H.; Ronco, A.; Olivera, L.; Kasdorf, H. Diet and adenocarcinoma of the lung: A case-control study in Uruguay. Lung Cancer 2002, 35, 43-51.
121. Brennan, P.; Fortes, C.; Butler, J.; Agudo, A.; Benhamou, S.; Darby, S.; Gerken, M.; Jökel, K.H.; Kreuzer, M.; Mallone, S.; et al. A multicenter case-control study of diet and lung cancer among non-smokers. Cancer Cause. Control 2000, 11, 49-58.
122. Garcia-Closas, R.; Agudo, A.; Gonzalez, C.A.; Agudo, A.; Riboli, E. Intake of specific carotenoids and flavonoids and the risk of lung cancer in women in Barcelona, Spain. Nutr. Cancer 1998, 32, 154-158.
123. Patterson, R.E.; White, E.; Kristal, A.R.; Neuhouser, M.L.; Potter, J.D. Vitamin supplements and cancer risk: The epidemiologic evidence. Cancer Cause. Control 1997, 8, 786-802.
124. Cooper, D.A.; Eldridge, A.L.; Peters, J.C. Dietary carotenoids and lung cancer: A review of recent research. Nutr Rev. 1999, 57, 133-145.
125. Mannisto, S.; Smith-Warner, S.A.; Spiegelman, D.; Albanes, D.; Anderson, K.; van den Brandt, P.A.; Cerhan, J.R.; Colditz, G.; Feskanich, D.; Freudenheim, J.L.; et al. Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies. Cancer Epidem. Biomarker. Prev. 2004, 13, 40-48.
126. Wright, M.E.; Mayne, S.T.; Swanson, C.A, Swanson, C.A.; Sinha, R.; Alavanja, M.C. Dietary carotenoids, vegetables, and lung cancer risk in women: The Missouri women's health study (United States). Cancer Cause. Control 2003, 14, 85-96.
127. Michaud, D.S.; Feskanich, D.; Rimm, E.B.; Colditz, G.A.; Speizer, F.E; Willett, W.C.; Giovannucci, E. Intake of specific carotenoids and risk of lung cancer in 2 prospective U.S. cohorts. Am. J. Clin. Nutr. 2000, 72, 990-997.
128. Bandera, E.V.; Freudenheim, J.L.; Marshall, J.R.; Zieleznv, M; Priore, R.L.; Brasure, J.; Baptiste, M.; Graham, S. Diet and alcohol consumption and lung cancer risk in the New York State Cohort (United States). Cancer Cause. Control 1997, 8, 828-840.
129. Holick, C.N.; Michaud, D.S.; Stolzenberg-Solomon, R.; Colditz, G.A.; Speizer, F.E.; Willett, W.C.; Giovannucci, E. Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the Alpha-Tocopherol, Beta-Carotene cohort study. Am. J. Epidemiol. 2002, 156, 536-547.
130. Rohan, T.E.; Jain, M.; Howe, G.R.; Miller, A.B. A cohort study of dietary carotenoids and lung cancer risk in women (Canada). Cancer Cause. Control 2002, 13, 231-237.
131. Satia, J.A; Littman, A.; Slatore, C.G.; Galanko, J.A.; White, E. Long-term use of b-carotene, retinol, lycopene, and lutein supplements and Lung cancer risk: Results from the VITamins and lifestyle (VITAL) study. Am. J. Epidemiol. 2009, 169, 815-828.
132. Gallicchio, L.; Boyd, K.; Matanoski, G.; Tao, X.G.; Chen, L.; Lam, T.K.; Shiels, M.; Hammond, E.; Robinson, K.A.; Caulfield, L.E.; et al. Carotenoids and the risk of developing lung cancer: A systematic review. Am. J. Clin. Nutr. 2008, 88, 372-383.
133. Wright, M.E.; Mayne, S.T.; Stolzenberg-Solomon, R.Z.; Li, Z.; Pietinen, P.; Taylor, P.R.; Virtamo, J.; Albanes, D. Development of a comprehensive dietary antioxidant index and application to lung cancer risk in a cohort of male smokers. Am. J. Epidemiol. 2004, 160, 68-76.
134. Yuan, J.M.; Stram, D.O.; Arakawa, K.; Lee, H.P.; Yu, M.C. Dietary cryptoxanthin and reduced risk of lung cancer: The Singapore Chinese Health Study. Cancer Epidem. Biomarker. Prev. 2003, 12, 890-898.
135. Neuhouser, M.L.; Patterson, R.E.; Thornquist, M.D.; Omenn, G.S.; King, I.B.; Goodman, G.E. Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the beta-carotene and retinol efficacy trial (CARET). Cancer Epidem. Biomarker. Prev. 2003, 12, 350-358.
136. Voorrips, L.E.; Goldbohm, R.A.; Brants, H.A.; van Poppel, G.A.; Sturmans, F.; Hermus, R.J.; van den Brandt, P.A. A prospective cohort study on antioxidant and folate intake and male lung cancer risk. Cancer Epidem. Biomarker. Prev. 2000, 9, 357-365.
137. Knekt, P.; Jarvinen, R.; Teppo, L.; Aromaa, A.; Seppanen, R. Role of various carotenoids in lung cancer prevention. J. Natl. Cancer Inss. 1999, 91, 182-184.
138. Yong, L.C.; Brown, C.C.; Schatzkin, A.; Dresser, C.M.; Slesinski, M.J.; Cox, C.S.; Taylor, P.R. Intake of vitamins E, C, and A and risk of lung cancer. The NHANES I epidemiologic followup study. First National Health and Nutrition Examination Survey. Am. J. Epidemiol. 1997, 146, 231-243.
139. Steinmetz, K.A.; Potter, J.D.; Folsom, A.R. Vegetables, fruit, and lung cancer in the Iowa Women's Health Study. Cancer Res. 1993, 53, 536-543.
140. Shekelle, R.B.; Tangney, C.C.; Rossof, A.H.; Stamler, J. Serum cholesterol, beta-carotene, and risk of lung cancer. Epidemiology 1992, 3, 282-287.
141. Shekelle, R.B.; Lepper, M.; Liu, S.; Maliza, C.; Raynor, W.J., Jr.; Rossof, A.H.; Paul, O.; Shryock, A.M.; Stamler, J. Dietary vitamin and risk of cancer in the Western Electric study. Lancet 1981, 2, 1185-1190.
142. Shibata, A.; Paganini-Hill, A.; Ross, R.K.; Henderson, B.E. Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: A prospective study. Br. J. Cancer 1992, 66, 673-679.
143. Shibata, A.; Paganini-Hill, A.; Ross, R.K.; Henderson, B.E. Dietary beta-carotene, cigarette smoking, and lung cancer in men. Cancer Cause. Control 1992, 3, 207-214.
144. Chow, W.H.; Schuman, L.M.; McLaughlin, J.K.; Bjelke, E.; Gridley, G.; Wacholder, S.; Chien, H.T.; Blot, W.J. A cohort study of tobacco use, diet, occupation, and lung cancer mortality. Cancer Cause. Control 1992, 3, 247-254.
145. Connett, J.E.; Kuller, L.H.; Kjelsberg, M.O.; Polk, B.F.; Collins, G.; Rider, A.; Hulley, S.B. Relationship between carotenoids and cancer. The Multiple Risk Factor Intervention Trial (MRFIT) Study. Cancer 1989, 64, 126-134.
146. Alfonso, H.S.; Fritschi, L.; de Klerk, N.H.; Ambrosini, G.L.; Beilby, J.; Olsen, N.; Musk, A.W. Plasma vitamin concentrations and incidence of mesothelioma and lung cancer in individuals exposed to crocidolite at Wittenoom, Western Australia. Eur. J. Cancer Prev. 2006, 15, 290-294.
147. Goodman, G.E.; Schaffer, S.; Omenn, G.S.; Chen, C.; King, I. The association between lung and prostate cancer risk, and serum micronutrients: Results and lessons learned from beta-carotene and retinol efficacy trial. Cancer Epidem. Biomarker. Prev. 2003, 12, 518-526.
148. Ratnasinghe, D.; Forman, M.R.; Tangrea, J.A.; Qiao, Y.; Yao, S.X.; Gunter, E.W.; Barrett, M.J.; Giffen, C.A.; Erozan, Y.; Tockman, M.S.; et al. Serum carotenoids are associated with increased lung cancer risk among alcohol drinkers, but not among non-drinkers in a cohort of tin miners. Alcohol Alcohol. 2000, 35, 355-360.
149. Comstock, G.W.; Alberg, A.J.; Huang, H.Y.; Wu, K.; Burke, A.E.; Hoffman, S.C.; Norkus, E.P.; Gross, M.; Cutler, R.G.; Morris, J.S.; et al. The risk of developing lung cancer associated with antioxidants in the blood: Ascorbic acid, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity. Cancer Epidem. Biomarker. Prev. 1997, 6, 907-916.
150. Menkes, M.S.; Comstock, G.W.; Vuilleumier, J.P.; Helsing, K.J.; Rider, A.A.; Brookmeyer, R. Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer. N. Engl. J. Med. 1986, 315, 1250-1254.
151. Orentreich, N.; Matias, J.R.; Vogelman, J.H.; Salkeld, R.M.; Bhagavan, H.; Friedman, G.D. The predictive value of serum beta-carotene for subsequent development of lung cancer. Nutr. Cancer 1991, 16, 167-176.
152. Knekt, P.; Aromaa, A.; Maatela, J.; Aaran, R.K.; Nikkari, T.; Hakama, M.; Hakulinen, T.; Peto, R.; Teppo, L. Serum vitamin A and subsequent risk of cancer: Cancer incidence follow-up of the Finnish Mobile Clinic Health Examination Survey. Am. J. Epidemiol. 1990, 132, 857-870.
153. Wald, N.J.; Thompson, S.G.; Densem, J.W.; Boreham, J.; Bailey, A. Serum beta-carotene and subsequent risk of cancer: Results from the BUPA Study. Br. J. Cancer 1988, 57, 428-433.
154. Nomura, A.M.; Stemmermann, G.N.; Heilbrun, L.K.; Salkeld, R.M.; Vuilleumier, J.P. Serum vitamin levels and the risk of cancer of specific sites in men of Japanese ancestry in Hawaii. Cancer Res. 1985, 45, 2369-2372.
155. Ito, Y.; Wakai, K.; Suzuki, K.; Ozasa, K.; Watanabe, Y.; Seki, N.; Ando, M.; Nishino, Y.; Kondo, T.; Ohno, Y.; Tamakoshi, A.; JACC Study Group. Lung cancer mortality and serum levels of carotenoids, retinol, tocopherols, and folic acid in men and women: a case-control study nested in the JACC Study. J. Epidemiol. 2005, 15, S140-S149.
156. Ito, Y.; Kurata, M.; Hioki, R.; Suzuki, K.; Ochiai, J.; Aoki, K. Cancer mortality and serum levels of carotenoids, retinol, and tocopherol: A populationbased follow-up study of inhabitants of a rural area of Japan. Asian Pac. J. Cancer Prev. 2005, 6, 10-15.
157. Eichholzer, M.; Stahelin, H.B.; Gey, K.F.; Ludin, E.; Bernasconi, F. Predictio of male cancer mortality by plasma levels of interacting vitamins: 17- year follow-up of the prospective Basel study. Int. J. Cancer 1996, 66, 145-150.
158. World Cancer Res Fund (WCRF) and the American Institute for Cancer Res (AICR). S, nutrition, physical activity, and the prevention of cancer: A global perspective. AICR: Washington DC, USA, 2007.