Lycopene metabolism and its biological significance

American Journal of Clinical Nutrition

Volumn 96, Issue 5, 2012, Pages

  Wang, Xiang Dong ^a  

^a TUFTS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA CAROTENE; BETA CAROTENE; BETA CRYPTOXANTHIN; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; LOW DENSITY LIPOPROTEIN; LYCOPENE; PHYTOENE SYNTHASE; RETINOID X RECEPTOR; SCAVENGER RECEPTOR BI; SOMATOMEDIN; SOMATOMEDIN BINDING PROTEIN 1; SOMATOMEDIN BINDING PROTEIN 6; TRANSCRIPTION FACTOR NRF2; VERY LOW DENSITY LIPOPROTEIN;

ANTIOXIDANT RESPONSIVE ELEMENT; APOPTOSIS; CELL CYCLE PROGRESSION; CELL PROLIFERATION; CHEMOPROPHYLAXIS; DETOXIFICATION; ENZYME SUBSTRATE COMPLEX; FATTY ACID OXIDATION; FOOD PROCESSING; HUMAN; LYCOPENE METABOLISM; MICHAELIS MENTEN KINETICS; NEGATIVE FEEDBACK; NONHUMAN; OXIDATIVE STRESS; PROTEIN BINDING; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; VITAMIN METABOLISM; VITAMIN SUPPLEMENTATION;

ANTIOXIDANTS; CAROTENOIDS; HUMANS; LYCOPERSICON ESCULENTUM; OXYGENASES; RECEPTORS, RETINOIC ACID;

EID: 84867822382     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.3945/ajcn.111.032359     Document Type: Review

References (104)

1. Britton G, Liaaen-Jensen S, Pfander H. Carotenoids handbook. Basel, Switzerland: Birkhäuser Verlag, 2004.
2. Story EN, Kopec RE, Schwartz SJ, Harris GK. An update on the health effects of tomato lycopene. Annu Rev Food Sci Technol 2010;1:189-210.
3. Wang XD. Carotenoids. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern nutrition in health and disease. 11th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2012:427-37.
4. Mein J, Wang XD. Oxidative metabolites of lycopene and their biological functions. In: Landrum JT, ed. Carotenoids. Boca Raton, FL: Taylor and Francis Group, 2010:417-35.
5. Lindshield BL, Canene-Adams K, Erdman JW Jr. Lycopenoids: are lycopene metabolites bioactive? Arch Biochem Biophys 2007;458:136-40. (Pubitemid 46215568)
6. Caris-Veyrat C. Formation of carotenoid oxygenaed cleavage products. In: Landrum JT, ed. Carotenoids. Boca Raton, FL: Taylor and Francis Group, 2010:215-28.
7. Kiefer C, Hessel S, Lampert JM, Vogt K, Lederer MO, Breithaupt DE, von Lintig J. Identification and characterization of a mammalian enzyme catalyzing the asymmetric oxidative cleavage of provitamin A. J Biol Chem 2001;276:14110-6.
8. Hu KQ, Liu C, Ernst H, Krinsky NI, Russell RM, Wang XD. The biochemical characterization of ferret carotene-9′,10′-monooxygenase catalyzing cleavage of carotenoids in vitro and in vivo. J Biol Chem 2006;281:19327-38. (Pubitemid 44035438)
9. Wang XD. Biological activities of carotenoid metabolites. In: Britton G, Liaaen-Jensen S, Pfander H, eds. Carotenoids. Basel, Switzerland: Birkhäuser Verlag, 2009:383-408.
10. Rock CL, Swendseid ME, Jacob RA, McKee RW. Plasma carotenoid levels in human subjects fed a low carotenoid diet. J Nutr 1992;122:96-100.
11. Lobo GP, Hessel S, Eichinger A, Noy N, Moise AR, Wyss A, Palczewski K, von Lintig J. ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production. FASEB J 2010;24:1656-66.
12. von Lintig J. Colors with functions: elucidating the biochemical and molecular basis of carotenoid metabolism. Annu Rev Nutr 2010;30:35-56.
13. Seino Y, Miki T, Kiyonari H, Abe T, Fujimoto W, Kimura K, Takeuchi A, Takahashi Y, Oiso Y, Iwanaga T, et al. ISX participates in the maintenance of vitamin A metabolism by regulation of beta-carotene 15,15′-monooxygenase (Bcmo1) expression. J Biol Chem 2008;283:4905-11.
14. Choi S, Koo S. Efficient syntheses of the keto-carotenoids canthaxanthin, astaxanthin, and astacene. J Org Chem 2005;70:3328-31. (Pubitemid 40547569)
15. During A, Harrison EH. Intestinal absorption and metabolism of carotenoids: insights from cell culture. Arch Biochem Biophys 2004;430:77-88. (Pubitemid 39119782)
16. Moussa M, Gouranton E, Gleize B, Yazidi CE, Niot I, Besnard P, Borel P, Landrier JF. CD36 is involved in lycopene and lutein uptake by adipocytes and adipose tissue cultures. Mol Nutr Food Res 2011;55:578-84.
17. Wang XD, Krinsky NI, Marini RP, Tang G, Yu J, Hurley R, Fox JG, Russell RM. Intestinal uptake and lymphatic absorption of betacarotene in ferrets: a model for human beta-carotene metabolism. Am J Physiol 1992;263:G480-6.
18. Canene-Adams K, Erdman JW. Absorption, transport, distribution in tissues and bioavailability. In: Britton G, Liaaen-Jensen S, Pfander H, eds. Carotenoids. Basel, Switzerland: Birkhäuser Verlag, 2009:115-48.
19. von Lintig J, Vogt K. Filling the gap in vitamin A research: molecular identification of an enzyme cleaving beta-carotene to retinal. J Biol Chem 2000;275:11915-20. (Pubitemid 30237761)
20. Leuenberger MG, Engeloch-Jarret C, Woggon WD. The reaction mechanism of the enzyme-catalyzed central cleavage of beta-carotene to retinal. Angew Chem Int Ed Engl 2001;40:2613-7.
21. Wyss A, Wirtz GM, Woggon WD, Brugger R, Wyss M, Friedlein A, Riss G, Bachmann H, Hunziker W. Expression pattern and localization of beta,beta-carotene 15,15′-dioxygenase in different tissues. Biochem J 2001;354:521-9. (Pubitemid 32269715)
22. Redmond TM, Gentleman S, Duncan T, Yu S, Wiggert B, Gantt E, Cunningham FX Jr. Identification, expression, and substrate specificity of a mammalian beta-carotene 15,15′-dioxygenase. J Biol Chem 2001;276:6560-5.
23. Lindqvist A, He YG, Andersson S. Cell type-specific expression of β-carotene 9′,10′-monooxygenase in human tissues. J Histochem Cytochem 2005;53:1403-12. (Pubitemid 41513072)
24. Lindqvist A, Dreja K, Sward K, Hellstrand P. Effects of oxygen tension on energetics of cultured vascular smooth muscle. Am J Physiol Heart Circ Physiol 2002;283:H110-7. (Pubitemid 34705330)
25. Lindqvist A, Andersson S. Biochemical properties of purified recombinant human beta-carotene 15,15′-monooxygenase. J Biol Chem 2002;277:23942-8. (Pubitemid 34952239)
26. Kim YS, Oh DK. Biotransformation of carotenoids to retinal by carotenoid 15,15′-oxygenase. Appl Microbiol Biotechnol 2010;88:807-16.
27. Poliakov E, Gentleman S, Cunningham FX Jr, Miller-Ihli NJ, Redmond TM. Key role of conserved histidines in recombinant mouse beta-carotene 15,15′-monooxygenase-1 activity. J Biol Chem 2005;280:29217-23. (Pubitemid 41161374)
28. Ganguly J, Sastry PS. Mechanism of conversion of beta-carotene into vitamin A - central cleavage versus random cleavage. World Rev Nutr Diet 1985;45:199-220.
29. Wang XD, Tang GW, Fox JG, Krinsky NI, Russell RM. Enzymatic conversion of beta-carotene into beta-apo-carotenals and retinoids by human, monkey, ferret, and rat tissues. Arch Biochem Biophys 1991;285:8-16.
30. Tang GW, Wang XD, Russell RM, Krinsky NI. Characterization of beta-apo-13-carotenone and beta-apo-14′-carotenal as enzymatic products of the excentric cleavage of beta-carotene. Biochemistry 1991;30:9829-34.
31. Amengual J, Lobo GP, Golczak M, Li HN, Klimova T, Hoppel CL, Wyss A, Palczewski K, von Lintig J. A mitochondrial enzyme degrades carotenoids and protects against oxidative stress. FASEB J 2011;25:948-59.
32. Lakshmanan MR, Pope JL, Olson JA. The specificity of a partially purified carotenoid cleavage enzyme of rabbit intestine. Biochem Biophys Res Commun 1968;33:347-52.
33. Liu C, Wang XD, Russell RM. Biosynthesis of retinoic acid from beta-apo-14′-carotenal in ferret in vivo. J Nutr Biochem 1997;8:652-7. (Pubitemid 27483661)
34. Wang XD, Russell RM, Liu C, Stickel F, Smith DE, Krinsky NI. Beta-oxidation in rabbit liver in vitro and in the perfused ferret liver contributes to retinoic acid biosynthesis from beta-apocarotenoic acids. J Biol Chem 1996;271:26490-8. (Pubitemid 26359046)
35. Wang XD, Marini RP, Hebuterne X, Fox JG, Krinsky NI, Russell RM. Vitamin E enhances the lymphatic transport of beta-carotene and its conversion to vitamin A in the ferret. Gastroenterology 1995;108:719-26.
36. Hébuterne X, Wang XD, Johnson EJ, Krinsky NI, Russell RM. Intestinal absorption and metabolism of 9-cis-beta-carotene in vivo: biosynthesis of 9-cis-retinoic acid. J Lipid Res 1995;36:1264-73.
37. Ho CC, de Moura FF, Kim SH, Clifford AJ. Excentral cleavage of beta-carotene in vivo in a healthy man. Am J Clin Nutr 2007;85:770-7. (Pubitemid 46393509)
38. Kopec RE, Riedl KM, Harrison EH, Curley RW Jr, Hruszkewycz DP, Clinton SK, Schwartz SJ. Identification and quantification of apolycopenals in fruits, vegetables, and human plasma. J Agric Food Chem 2010;58:3290-6.
39. Hessel S, Eichinger A, Isken A, Amengual J, Hunzelmann S, Hoeller U, Elste V, Hunziker W, Goralczyk R, Oberhauser V, et al. CMO1 deficiency abolishes vitamin A production from beta-carotene and alters lipid metabolism in mice. J Biol Chem 2007;282:33553-61. (Pubitemid 350159522)
40. Berry SD, Davis SR, Beattie EM, Thomas NL, Burrett AK, Ward HE, Stanfield AM, Biswas M, Ankersmit-Udy AE, Oxley PE, et al. Mutation in bovine beta-carotene oxygenase 2 affects milk color. Genetics 2009;182:923-6.
41. Tian B, Sun Z, Shen S, Wang H, Jiao J, Wang L, Hu Y, Hua Y. Effects of carotenoids from Deinococcus radiodurans on protein oxidation. Lett Appl Microbiol 2009;49:689-94.
42. Mein JR, Dolnikowski GG, Ernst H, Russell RM, Wang XD. Enzymatic formation of apo-carotenoids from the xanthophyll carotenoids lutein, zeaxanthin and beta-cryptoxanthin by ferret carotene-9′,10′-monooxygenase. Arch Biochem Biophys 2011;506:109-21.
43. Mein JR, Lian F, Wang XD. Biological activity of lycopene metabolites: implications for cancer prevention. Nutr Rev 2008;66:667-83.
44. Boileau AC, Merchen NR, Wasson K, Atkinson CA, Erdman JW Jr. cis-Lycopene is more bioavailable than trans-lycopene in vitro and in vivo in lymph-cannulated ferrets. J Nutr 1999;129:1176-81. (Pubitemid 29250167)
45. Liu C, Lian F, Smith DE, Russell RM, Wang XD. 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;63:3138-44. (Pubitemid 36735865)
46. Våge DI, Boman IA. A nonsense mutation in the beta-carotene oxygenase 2 (BCO2) gene is tightly associated with accumulation of carotenoids in adipose tissue in sheep (Ovis aries). BMC Genet 2010;11:10.
47. Eriksson J, Larson G, Gunnarsson U, Bed'hom B, Tixier-Boichard M, Stromstedt L, Wright D, Jungerius A, Vereijken A, Randi E, et al. Identification of the yellow skin gene reveals a hybrid origin of the domestic chicken. PLoS Genet 2008;4:e1000010.
48. Castañeda MP, Hirschler EM, Sams AR. Skin pigmentation evaluation in broilers fed natural and synthetic pigments. Poult Sci 2005;84:143-7. (Pubitemid 40134377)
49. Khachik F. Chemical and metabolic oxidation of carotenoids. In: Packer L, Kraemer K, Obermuller-Jevic U, Sies H, eds. Carotenoids and retinoids: molecular aspects and health issues. Champaign, IL: AOCS Press, 2005:61-75.
50. Gajic M, Zaripheh S, Sun F, Erdman JW Jr. Apo-8′-lycopenal and apo-12′-lycopenal are metabolic products of lycopene in rat liver. J Nutr 2006;136:1552-7. (Pubitemid 43765361)
51. Reynaud E, Aydemir G, Ruhl R, Dangles O, Caris-Veyrat C. Organic synthesis of new putative lycopene metabolites and preliminary investigation of their cell-signaling effects. J Agric Food Chem 2011;59:1457-63.
52. Palozza P, Parrone N, Catalano A, Simone R. Tomato lycopene and inflammatory cascade: basic interactions and clinical implications. Curr Med Chem 2010;17:2547-63.
53. Kelkel M, Schumacher M, Dicato M, Diederich M. Antioxidant and anti-proliferative properties of lycopene. Free Radic Res 2011;45:925-40.
54. Kensler TW, Wakabayashi N. Nrf2: friend or foe for chemoprevention? Carcinogenesis 2010;31:90-9.
55. Wakabayashi N, Slocum SL, Skoko JJ, Shin S, Kensler TW. When NRF2 talks, who's listening? Antioxid Redox Signal 2010;13:1649-63.
56. 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;4:177-86. (Pubitemid 40268075)
57. Lian F, Smith DE, Ernst H, Russell RM, Wang XD. Apo-10′-lycopenoic acid inhibits lung cancer cell growth in vitro, and suppresses lung tumorigenesis in the A/J mouse model in vivo. Carcinogenesis 2007;28:1567-74. (Pubitemid 47241807)
58. Gradelet S, Astorg P, Leclerc J, Chevalier J, Vernevaut MF, Siess MH. Effects of canthaxanthin, astaxanthin, lycopene and lutein on liver xenobiotic-metabolizing enzymes in the rat. Xenobiotica 1996;26:49-63. (Pubitemid 26108102)
59. Wang Y, Ausman LM, Greenberg AS, Russell RM, Wang XD. Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis- promoted hepatocarcinogenesis in rats. Int J Cancer 2010;126:1788-96.
60. Lian F, Wang XD. Enzymatic metabolites of lycopene induce Nrf2-mediated expression of phase II detoxifying/antioxidant enzymes in human bronchial epithelial cells. Int J Cancer 2008;123:1262-8.
61. Mandal P, Park PH, McMullen MR, Pratt BT, Nagy LE. The antiinflammatory effects of adiponectin are mediated via a heme oxygenase-1-dependent pathway in rat Kupffer cells. Hepatology 2010;51:1420-9.
62. Mandal P, Pritchard MT, Nagy LE. Anti-inflammatory pathways and alcoholic liver disease: role of an adiponectin/interleukin-10/heme oxygenase-1 pathway. World J Gastroenterol 2010;16:1330-6.
63. World Health Organization. International classification of diseases: manual of the international statistical classification of diseases, injuries, and causes of death., Vol. 1, 9th rev. Geneva, Switzerland: World Health Organization, 1977.
64. Napoli JL, Race KR. Biogenesis of retinoic acid from beta-carotene: differences between the metabolism of beta-carotene and retinal. J Biol Chem 1988;263:17372-7.
65. Wang XD, Krinsky NI, Benotti PN, Russell RM. Biosynthesis of 9-cis-retinoic acid from 9-cis-′-carotene in human intestinal mucosa in vitro. Arch Biochem Biophys 1994;313:150-5. (Pubitemid 24261103)
66. Kim Y, Lian F, Yeum KJ, Chongviriyaphan N, Choi SW, Russell RM, Wang XD. The effects of combined antioxidant (beta-carotene, alpha-tocopherol and ascorbic acid) supplementation on antioxidant capacity, DNA single-strand breaks and levels of insulin-like growth factor-1/IGF-binding protein 3 in the ferret model of lung cancer. Int J Cancer 2007;120:1847-54. (Pubitemid 46418359)
67. Prakash P, Liu C, Hu KQ, Krinsky NI, Russell RM, Wang XD. Betacarotene and beta-apo-14′-carotenoic acid prevent the reduction of retinoic acid receptor beta in benzo[a]pyrene-treated normal human bronchial epithelial cells. J Nutr 2004;134:667-73. (Pubitemid 38298514)
68. Wang XD. Carotenoid oxidative/degradative products and their biological activities. In: Krinsky NI, Mayne ST, Sies H, eds. Carotenoids in health and disease. New York, NY: Marcel Dekker, 2004:313-35.
69. Eroglu A, Hruszkewycz DP, Curley RW Jr, Harrison EH. The eccentric cleavage product of beta-carotene, beta-apo-13-carotenone, functions as an antagonist of RXRalpha. Arch Biochem Biophys 2010.
70. Shmarakov I, Fleshman MK, D'Ambrosio DN, Piantedosi R, Riedl KM, Schwartz SJ, Curley RW Jr, von Lintig J, Rubin LP, Harrison EH, et al. Hepatic stellate cells are an important cellular site for betacarotene conversion to retinoid. Arch Biochem Biophys 2010;504:3-10.
71. Suzuki T, Matsui M, Murayama A. Biological activity of (all-E)-beta-apo-12′-carotenoic acid and the geometrical isomers on human acute promyelocytic leukemia cell line HL-60. J Nutr Sci Vitaminol (Tokyo) 1995;41:575-85. (Pubitemid 26048710)
72. Tibaduiza EC, Fleet JC, Russell RM, Krinsky NI. Excentric cleavage products of beta-carotene inhibit estrogen receptor positive and negative breast tumor cell growth in vitro and inhibit activator protein-1-mediated transcriptional activation. J Nutr 2002;132:1368-75. (Pubitemid 34606478)
73. 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;47:659-67.
74. Winum JY, Kamal M, Defacque H, Commes T, Chavis C, Lucas M, Marti J, Montero JL. Synthesis and biological activities of higher homologues of retinoic acid. Farmaco 1997;52:39-42. (Pubitemid 27240173)
75. Ziouzenkova O, Orasanu G, Sukhova G, Lau E, Berger JP, Tang G, Krinsky NI, Dolnikowski GG, Plutzky J. Asymmetric cleavage of beta-carotene yields a transcriptional repressor of retinoid X receptor and peroxisome proliferator-activated receptor responses. Mol Endocrinol 2007;21:77-88. (Pubitemid 46041692)
76. Duncan RE, Lau D, El-Sohemy A, Archer MC. Geraniol and betaionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity. Biochem Pharmacol 2004;68:1739-47. (Pubitemid 39278496)
77. Liu JR, Dong HW, Sun XR, Wang Q, Sun WG, Parry JW, Liu Q, Han XH, Sun CH, Chen BQ, et al. Effects of beta-ionone on mammary carcinogenesis and antioxidant status in rats treated with DMBA. Nutr Cancer 2010;62:58-65.
78. Jung M, Mo H, Elson CE. Synthesis and biological activity of beta-ionone-derived alcohols for cancer chemoprevention. Anticancer Res 1998;18:189-92. (Pubitemid 28174705)
79. Liu JR, Sun XR, Dong HW, Sun CH, Sun WG, Chen BQ, Song YQ, Yang BF. Beta-ionone suppresses mammary carcinogenesis, proliferative activity and induces apoptosis in the mammary gland of the Sprague-Dawley rat. Int J Cancer 2008;122:2689-98. (Pubitemid 351631370)
80. Lian F, Hu KQ, Russell RM, Wang XD. Beta-cryptoxanthin suppresses the growth of immortalized human bronchial epithelial cells and non-small-cell lung cancer cells and up-regulates retinoic acid receptor beta expression. Int J Cancer 2006;119:2084-9. (Pubitemid 44423665)
81. Matsumoto A, Mizukami H, Mizuno S, Umegaki K, Nishikawa J, Shudo K, Kagechika H, Inoue M. Beta-cryptoxanthin, a novel natural RAR ligand, induces ATP-binding cassette transporters in macrophages. Biochem Pharmacol 2007;74:256-64. (Pubitemid 46900810)
82. Nara E, Hayashi H, Kotake M, Miyashita K, Nagao A. Acyclic carotenoids and their oxidation mixtures inhibit the growth of HL-60 human promyelocytic leukemia cells. Nutr Cancer 2001;39:273-83. (Pubitemid 33694047)
83. Ben-Dor A, Nahum A, Danilenko M, Giat Y, Stahl W, Martin HD, Emmerich T, Noy N, Levy J, Sharoni Y. Effects of acyclo-retinoic acid and lycopene on activation of the retinoic acid receptor and proliferation of mammary cancer cells. Arch Biochem Biophys 2001;391:295-302. (Pubitemid 32662272)
84. Kotake-Nara E, Kushiro M, Zhang H, Sugawara T, Miyashita K, Nagao A. Carotenoids affect proliferation of human prostate cancer cells. J Nutr 2001;131:3303-6. (Pubitemid 33136153)
85. Kotake-Nara E, Kim SJ, Kobori M, Miyashita K, Nagao A. Acycloretinoic acid induces apoptosis in human prostate cancer cells. Anticancer Res 2002;22:689-95. (Pubitemid 34475215)
86. Stahl W, von Laar J, Martin HD, Emmerich T, Sies H. Stimulation of gap junctional communication: comparison of acyclo-retinoic acid and lycopene. Arch Biochem Biophys 2000;373:271-4. (Pubitemid 30046514)
87. de Thé H, Vivanco-Ruiz MM, Tiollais P, Stunnenberg H, Dejean A. Identification of a retinoic acid responsive element in the retinoic acid receptor beta gene. Nature 1990;343:177-80.
88. Herzog A, Siler U, Spitzer V, Seifert N, Denelavas A, Hunziker PB, Hunziker W, Goralczyk R, Wertz K. Lycopene reduced gene expression of steroid targets and inflammatory markers in normal rat prostate. FASEB J 2005;19:272-4. (Pubitemid 40189279)
89. 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;18:1019-21. (Pubitemid 39561511)
90. Hirsch K, Atzmon A, Danilenko M, Levy J, Sharoni Y. Lycopene and other carotenoids inhibit estrogenic activity of 17beta-estradiol and genistein in cancer cells. Breast Cancer Res Treat 2007;104:221-30. (Pubitemid 47084226)
91. Karas M, Amir H, Fishman D, Danilenko M, Segal S, Nahum A, Koifmann A, Giat Y, Levy J, Sharoni Y. Lycopene interferes with cell cycle progression and insulin-like growth factor I signaling in mammary cancer cells. Nutr Cancer 2000;36:101-11. (Pubitemid 30317841)
92. Levy J, Bosin E, Feldman B, Giat Y, Miinster A, Danilenko M, Sharoni Y. Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta-carotene. Nutr Cancer 1995;24:257-66.
93. Jones JI, Clemmons D. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 1995;16:3-34.
94. Nahum A, Zeller L, Danilenko M, Prall OW, Watts CK, Sutherland RL, Levy J, Sharoni Y. Lycopene inhibition of IGF-induced cancer cell growth depends on the level of cyclin D1. Eur J Nutr 2006;45:275-82. (Pubitemid 44167661)
95. Mucci LA, Tamimi R, Lagiou P, Trichopoulou A, Benetou V, Spanos E, Trichopoulos D. Are dietary influences on the risk of prostate cancer mediated through the insulin-like growth factor system? BJU Int 2001;87:814-20. (Pubitemid 34204321)
96. Holmes MD, Pollak MN, Hankinson SE. Lifestyle correlates of plasma insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations. Cancer Epidemiol Biomarkers Prev 2002;11:862-7. (Pubitemid 35014889)
97. Yu H, Spitz MR, Mistry J, Gu J, Hong WK, Wu X. Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis. J Natl Cancer Inst 1999;91:151-6. (Pubitemid 29042692)
98. London SJ, Yuan JM, Travlos GS, Gao YT, Wilson RE, Ross RK, Yu MC. Insulin-like growth factor I, IGF-binding protein 3, and lung cancer risk in a prospective study of men in China. J Natl Cancer Inst 2002;94:749-54. (Pubitemid 34567959)
99. Wakai K, Ito Y, Suzuki K, Tamakoshi A, Seki N, Ando M, Ozasa K, Watanabe Y, Kondo T, Nishino Y, et al. Serum insulin-like growth factors, insulin-like growth factor-binding protein-3, and risk of lung cancer death: a case-control study nested in the Japan Collaborative Cohort (JACC) Study. Jpn J Cancer Res 2002;93:1279-86. (Pubitemid 36104866)
100. Wang XD. Can smoke-exposed ferrets be utilized to unravel the mechanisms of action of lycopene? J Nutr 2005;135:2053S-6S.
101. Chung J, Koo K, Lian F, Hu KQ, Ernst H, Wang XD. Apo-10′-lycopenoic acid, a lycopene metabolite, increases sirtuin 1 mRNA and protein levels and decreases hepatic fat accumulation in ob/ob mice. J Nutr 2012;142:405-10.
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;41:1399-407. (Pubitemid 37289189)
103. 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;35:1653-63. (Pubitemid 37532916)
104. Ford NA, Elsen AC, Zuniga K, Lindshield BL, Erdman JW Jr. Lycopene and apo-12′-lycopenal reduce cell proliferation and alter cell cycle progression in human prostate cancer cells. Nutr Cancer 2011;63:256-63.