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Effects of Tomatoes and Lycopene on Prostate Cancer Prevention and Treatment

토마토와 라이코펜이 전립선암의 예방과 치료에 미치는 영향

  • ;
  • Phyllis E. Bowen
  • 황은선 (서울대학교 농업생물신소재연구센터) ;
  • Published : 2004.02.01

Abstract

Prostate cancer is a leading cause of cancer death in American men and evidences point to significant life style/diet components as risk factors for its development or prevention. Two large cohort studies have identified the consumption of tomatoes or high Plasma levels of Iycopene as associated with reduced risk. A number of other substances such as quercetin, phytoene, phytofluene, cyclolycopene, salicylates and tomatine in tomato besides lycopene could have anticancer activity and may be acting synergistically with lycopene. Lycopene at almost physiologically feasible concentrations, reduces cell viability by cell cycle arrest and apoptosis and modulates the cyclin pathways as well as increasing intercellular communication. However, it is not clear whether lycopene or its oxidation products are more bioactive. Tomato product supplementation results in plasma accumulation of phytoene, Phytofluene, the lycopene oxidation product, and cyclolycopene at significant concentrations and lycopene supplementation, either as a tomato product or as beadlets, results in maximal mean plasma lycopene concentrations of ∼ 1 $\mu$M which is at the lower limit of its activity in cell culture. Rats and mice are poor accumulators of lycopene and other carotenoids making them poor models for the study of cancer prevention and control. Of the 19 animal studies for various cancer sites, lycopene showed a positive effect in 10 studies but negative in 2 prostate cancer studies. In vivo prevention of leukocyte DNA damage in humans has been mostly studied using tomato product supplementation but lycopene supplementation appeared to reduce oxidative DNA damage as well as tomato product supplementation. Lycopene appears to be bioactive in intefering with carcinogenesis but the actions of phytoene, phytofluene or cyclolycopene cannot be ruled out since these compounds were present in most of the lycopene material used for these studies. Although lycopene remains as a promising agent, especially for cancer control, exploring interactions with other tomato phytochemicals and with current prostate cancer therapies should be encouraged.

토마토에는 라이코펜과 quercetin, phytoene, phytofluene, cyclolycopene, salicylates 그리고 tomatlne과 같은 다양한 생리활성 물질들이 함유되어 있으며, 이들은 라이코펜과 함께 항암작용에 관여하는 것으로 사료된다. 생리적 농도에서 라이코펜은 세포주기의 정지(arrest)와 세포 자가사멸을 통한 암세포의 생존률을 감소시키고, 사이클린을 조절하며, 세포간의 연락체계를 증가시키는 것으로 보고되고 있다. 라이코펜은 산화에 민감하여 매우 쉽게 산화물질을 만든다. 토마토 제품의 섭취는 혈중 phytoene, phytofluene 그리고 라이코펜 산화물질인 cyclolycopene의 농도를 유의적으로 증가시켰다. 또한 토마토나 토마토 제품을 통한 라이코펜의 섭취는 혈중 라이코펜의 농도를 최고 1.26 $\mu$M까지 증가시켰다. 다양한 암 부위 (cancer sites)를 통한 19건의 동물실험결과, 10건의 실험에서 라이코펜이 효과가 입증되었고, 7건의 실험에서는 통계적인 유의성이 밝혀지지 않았고, 2건의 전립선암 실험에서는 억제효과를 보이지 않았다. 임상실험에서 라이코펜 섭취와 토마토 제품섭취군 모두 백혈구와 전립선에서 의 DNA 산화물질을 감소시킴을 확인하였다. 라이코펜은 암화과정을 방해하는 생리활성 물질로 밝혀졌으나 phytoene, phytofluene 그리고 cyclolycopene의 역할에 관해서는 아직 밝혀져 있지 않다. 따라서 라이코펜과 토마토에 함유되어 있는 다른 식물성 화학성분들(phytochemicals) 간의 상호작용에 관해서는 좀 더 구체적이고 신뢰성 있는 연구가 필요하다.

Keywords

References

  1. Kalish LA, McDougal WS, McKinlay JB. 1995. Family history and the risk of prostate cancer. Urology 56: 803-806. https://doi.org/10.1016/S0090-4295(00)00780-9
  2. American Institute of Cancer Research. 1997. Food, Nutrition and the Prevention of Cancer: A Global Perspective. Banta Book Group, Manasha.WI.
  3. National Cancer Institute (US). 1999. Prostate cancer trends 1973-1995. NIH Publ No. 99-9543; SEER Monograph. Bethesda, MD: National Cancer Institute. p 1-56.
  4. Burks D, Littleton R. 1992. The epidemiology of prostate cancer in black men. Henry Ford Hosp Med J 40: 89-92.
  5. Angwafo FF. 1998. Migration and prostate cancer: an international perspective. J Natl Med Assoc 90: S720-S723.
  6. 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. https://doi.org/10.1093/jnci/87.23.1767
  7. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. 2002. A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst 94: 391-398. https://doi.org/10.1093/jnci/94.5.391
  8. Arab L, Steck-Scott S, Bowen P. 2001. Participation of lycopene and beta-carotene in carcinogenesis: defenders, aggressors, or passive bystanders? Epidemiol Rev 23: 211-230. https://doi.org/10.1093/oxfordjournals.epirev.a000803
  9. Rock CL, Flatt SW, Wright FA. 1997. Responsiveness of carotenoids to high vegetable diet intervention designed to prevent breast cancer recurrence. Cancer Epidemiol Biomarkers Prev 6: 617-623.
  10. Di Mascio P, Kaiser S, Sies H. 1989. Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch Biochem Soc Trans 24: 1023-1027.
  11. Pannala AS, Rice-Evans C, Sampson J, Singh S. 1998. Interaction of peroxynitrite with carotenoids and tocopherols within low density lipoprotein. FEBS Letters 423: 297-301. https://doi.org/10.1016/S0014-5793(98)00108-2
  12. Friedman M. 2002. Tomato glycoalkaloids: role in the plant and in the diet. J Agric Food Chem 50: 5751-5760. https://doi.org/10.1021/jf020560c
  13. Culig Z, Klocker H, Bartsch G, Hobisch A. 2002. Androgen receptors in prostate cancer. Endocr Relat Cancer 9: 155-170. https://doi.org/10.1677/erc.0.0090155
  14. Xing N, Chen Y, Mitchell SH, Young CV. 2001. Quercetin inhibits the expression and function of the androgen receptor in LNCap prostate cancer cells. Carcinogenesis 22: 409-414. https://doi.org/10.1093/carcin/22.3.409
  15. Swain AR, Dutton SP, Truswell AS. 1985. Salicylates in foods. J Amer Diet Assoc 85: 950-960.
  16. Navarro D, Luzardo OP, Fernandez L, Chesa N, Diaz-Chico BN. 2002. Transition to androgen-independence in prostate cancer. J Steroid Biochem Mol Biol 81: 191-201. https://doi.org/10.1016/S0960-0760(02)00064-X
  17. Williams AW, Boileau TWM, Clinton SK, Erdman JW. 2000. ${\beta}$-Carotene stability and uptake by prostate cancer cells are dependent on delivery vehicle. Nutr Cancer 36: 185-190. https://doi.org/10.1207/S15327914NC3602_7
  18. Levy J, Bosin E, Feldman B, Giat Y, Miinster A, Danilenko M, Sharoni Y. 1995. Lycopene is a more potent inhibitor of human cell proliferation than either ${\alpha}$-carotene or ${\beta}$-carotene. Nutr Cancer 24: 257-266. https://doi.org/10.1080/01635589509514415
  19. Kotake-Nara E, Kushiro M, Zhang H, Sugawara T, Myashita K, Nagao A. 2001. Carotenoids affect proliferationof human prostate cancer cells. J Nutr 131: 3303-3306.
  20. Hwang E, Bowen PE. 2003. Growth inhibition, cell-cycle arrest and apoptosis in LNCaP human prostate cancer cells by tomato paste extracts lycopene. J Nutr In press.
  21. Yeh SL, Hu ML. 2001. Induction of oxidative DNA damage in human foreskin fibroblast Hs68 cells by oxidized - carotene and lycopene. Free Rad Res 35: 203-213. https://doi.org/10.1080/10715760100300751
  22. Nara E, Hayashi H, Kotake M, Miyashita K, Nagao A. 2001. Acyclic carotenoids and their oxidation mixtures inhibit the growth of HL-60 human promyelocytic leukemia cells. Nutr Cancer 39: 273-283. https://doi.org/10.1207/S15327914nc392_18
  23. Khachik F, Steck A, Niggli UA, Pfander H. 1998. Partial synthesis and structural elucidation of the oxidative metabolites of lycopene identified in tomato paste, tomato juice and human serum. J Agric Food Chem 46: 4874-4884. https://doi.org/10.1021/jf980322a
  24. Palozza P. 1998. Prooxidant actions of carotenoids in biologic systems. Nutr Rev 56: 257-265. https://doi.org/10.1111/j.1753-4887.1998.tb01762.x
  25. Lowe GM, Booth LA, Young AJ, Cilton RF. 1999. Lycopene and ${\beta}$-carotene protect against oxidative damage in HT29 cells at low concentrations but rapidly lose this capacity at higher doses. Free Rad Res 30: 141-151. https://doi.org/10.1080/10715769900300151
  26. Matos HR, Di Mascio P, Medeiros HG. 2000. Protective effect of lycopene on lipid peroxidation and oxidative DNA damage in cell culture. Arch Biochem Biophys 383: 56-59. https://doi.org/10.1006/abbi.2000.2035
  27. Nahum A, Hirsch K, Danilenko M, Watts CKW, Prall OWJ, 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 p27Kip1 in the cyclin E cdk2 complexes. Oncogene 20: 3428-3436. https://doi.org/10.1038/sj.onc.1204452
  28. Livny O, Kaplan I, Reifen R, Polak-Charcon S, Mader Z, Schwartz B. 2002. Lycopene inhibits proliferation and enhances gap-junction communication of KB-1 human oral tumor cells. J Nutr 132: 3754-3759.
  29. Knowles LM, Zigrossi DA, Tauber RA, Hightower C, Milner JA. 2000. Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutr Cancer 38: 116-122. https://doi.org/10.1207/S15327914NC381_16
  30. Bhuvaneswari V, Velmurugan B, Balsenthil 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
  31. Velmurugan B, Bhuvaneswari V, Burra UK, Nagini S. 2002. Prevention of N-methyl-N'-nitro-N-nitrosoguanidine and saturated sodium chloride-induced gastric carcinogenesis in Wistar rats by lycopene. Eur J Cancer Prev 11: 19-26. https://doi.org/10.1097/00008469-200202000-00004
  32. Bhuvaneswari V, Velmurugan B, Nagini S. 2002. Induction of glutathione-dependent hepatic biotransformation enzymes by lycopene in the hamster cheek pouch carcinogenesis model. J Biochem Mol Biol Biophys 6: 257-260.
  33. Velmurugan B, Bhuvaneswari V, Nagini S. 2002. Antiperoxidative effects of lycopene during N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis. Fitoterapia 73: 604-611. https://doi.org/10.1016/S0367-326X(02)00216-2
  34. Wargovich MJ, Jimenz A, McKee K, Steele VE, Velasco M, Woods J, Rice R, Gray K, Kelloff GJ. 2000. Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression. Carcinogenesis 21: 1149-1155. https://doi.org/10.1093/carcin/21.6.1149
  35. Narisaws T, Fukaura Y, Hasebe M, Ito M, Aizawa R, Murakoshi M, Uemura SH, Khachic F, Nishimo H. 1996. Inhibitory effects of natural carotenoids, ${\alpha}$-carotene, ${\beta}$-carotene, lycopene and lutein, on colonic aberrant crypt foci formation in rats. Cancer Letters 107: 137-142. https://doi.org/10.1016/0304-3835(96)04354-6
  36. Kim JM, Araki S, Kim DJ, Park CB, Takasuka N, Baba-Toriyama H, Ota T, Nir Z, Khachik F, Shimidzu N, Tanaka Y, Osawa T, Uraji T, Murakoshi M, Nishimo H, Tsuda H. 1998. Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation. Carcinogenesis 19: 81-85. https://doi.org/10.1093/carcin/19.1.81
  37. Watanabe S, Kitade Y, Masaki T, Nishioka M, Satoh M, Satoh K, Nishino H. 2001. Effects of lycopene and Shosako-to on heptaocarcinogenesis in a rat model of spontaneous liver cancer. Nutr Cancer 39: 96-101. https://doi.org/10.1207/S15327914nc391_13
  38. Gradelet S, LeBon AM, Berges R, Suschetet M, Astorg P. 1998. Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DNA damage in the rate: role of the modulation of aflatoxiin B1 metabolism. Carcinogenesis 19: 403-411. https://doi.org/10.1093/carcin/19.3.403
  39. Astorg P, Gradelet S, Berges R, Suschetet M. 1997. Dietary lycopene decreases the initiation of liver preneoplastic foci by diethelnitrosamine in the rat. Nutr Cancer 29: 60-68. https://doi.org/10.1080/01635589709514603
  40. Kim DJ, Takasuka N, Nishino H, Tsuda H. 2000. Chemoprevention of lung cancer by lycopene. Biofactors 13: 95-102. https://doi.org/10.1002/biof.5520130116
  41. Hecht SS, Kenny PM, Wang M, Trushin N, Agarwal S, Rao AV, Upadhyaya P. 1999. Evaluation of butylated hydroxyanisole, myo-inositol, curcumin, esculetin, resveratrol and lycopene as inhibitors of benso(a)pyrene plus 4-(methylnitrosamino)-1-1(3-pyridyl)-1-butanone-induced lung tumorignenesis in A/J mice. Cancer Lett 137: 123-130. https://doi.org/10.1016/S0304-3835(98)00326-7
  42. 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, NMU and DMH. Cancer Lett 120: 15-22. https://doi.org/10.1016/S0304-3835(97)00281-4
  43. Guttenplan JB, Chen M, Koinska W, Thompson S, Zhao Z, Cohen LA. 2001. 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 163: 1-6. https://doi.org/10.1016/S0304-3835(00)00694-7
  44. Cohen LA, Zhao Z, Pittman B, Khachik F. 1999. Effect of dietary lycopene on N-nethylnitrosourea-induced mammary tumorigenesis. Nutr Cancer 34: 153-159. https://doi.org/10.1207/S15327914NC3402_5
  45. 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.
  46. Nagasawa H, Mitamura T, Sakamoto S, Yamamoto K. 1995. Effects of lycopene on spontaneous mammary tumour development of SHN virgin mice. Anticancer Res 15: 1173-1178.
  47. Okajima E, Ozono S, Endo T, Majima T, Tsutsumi M, Fukuda T, Akai H, Denda A, Hirao Y, Okajima E, Nishino H, Nir Z, Konishi Y. 1997. Chemopreventive efficacy of piroxicam administered alone or in combination with lycopene and beta-carotene on the development of ratu unrinary bladder carcinoma after N-butyl-N-(4-hydroxybutyl)nitrosamine treatment. Jpn J Cancer Res 88: 543-552. https://doi.org/10.1111/j.1349-7006.1997.tb00417.x
  48. Okajima E, Tsutsumi M, Osono S, Akai H, Denda A, Nishino H, Oshima S, Sakamoto H, Konishi Y. 1998. Inhibitory effect of tomato juice on rat urinary bladder carcinogenesis after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation. Jpn J Cancer Res 89: 22-26. https://doi.org/10.1111/j.1349-7006.1998.tb00474.x
  49. Imaida K, Tamano S, Kato K, Ikeda Y, Asamoto M, Takahashi S, Nir Z, Murakoshi M, Nishino H, Shirai T. 2001. Lack of chemopreventive effects of lycopene and curcumin on experimental rat prostate carcinogenesis. Carcinogenesis 22: 467-472. https://doi.org/10.1093/carcin/22.3.467
  50. Slifka KA, Bowen PE, Stacewicz-Sapuntzakis M, Cirssey SD. 1999. A survey of serum and dietary carotenoids in captive wild animals. J Nutr 129: 380-390.
  51. Boileau TWM, Clinton SK, Erdman JW. 2000. Tissue lycopene concentrations and isomer patterns are affected by androgen status and dietary lycopene concentratioonin male F344 rats. J Nutr 130: 1613-1618.
  52. Porrini M, Riso P. 2000. Lymphocyte lycopene concentration and DNA protection from oxidative damage is increased in women after a short period of tomato supplementation. J Nutr 130: 189-192.
  53. Riso P, Pinder A, Santangelo A, Porrini M. 1999. Does tomato consumption effectivelyincrease the resistance of lymphocyte DNA to oxidative damage? Am J Clin Nutr 69: 712-718.
  54. Rao AV, Agarwal S. 1998. Bioavailability and in vivo antioxidant properties of lycopene from tomato products and their possible role in the prevention of cancer. Nutri Cancer 31: 199-203. https://doi.org/10.1080/01635589809514703
  55. Paetau I, Khachik F, Brown ED, Beecher GR, Kramer TR, Chittams J, Clevidence BA. 1998. Chronic ingestion of lycopene-rich tomato juice or lycopene supplements significantly increases plasma concentrations of lycopene and related tomato carotenoids in humans. Am J Clin Nutr 68: 1187-1195.
  56. Chen G, Djuric Z. 2002. Detection of 2,6-cyclolycopene-1,5 diol in breast nipple aspirate fluids and plasma: a potential marker of oxidative stress. Cancer Epidemiol Biomarkers Prev 11: 1592-1596.
  57. Diwadlkar-Navsariwala V, Gustin DM, Rodvold KA, Sosman JA, Stacewicz-Sapuntzakis M, Murray JL, Tiller PA, Bowen PE. 2001. Single dose pharmacokinetics of tomato-based lycopene in healthy men. FASEB J 15: A297.
  58. Diwadlkar-Navsariwala V, Novotny JA, Gustin DM, Sosman JA, Stacewicz-Sapuntzakis M, Murray JL, Tiller PA, Bowen PE. 2000. Compartmental analysis of the dynamics of lycopene metabolism in healthy men. FASEB J 16: A603.
  59. Kucuk O, Sarkar FH, Sakr W, Djuric Z, Pollak MN, Khachik F, Li YW, Banerjee M, Grignon D, Bertram JS, Crissman JD, Pontes EJ, Wood DP. 2001. Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev 10: 861-868.
  60. Chen L, Stacewicz-Sapuntzakis M, Duncan C, Sharifi R, Ghosh L, van Breemen R, Ashton D, Bowen PE. 2001. Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention. J Natl Cancer Inst 93: 1872-1879. https://doi.org/10.1093/jnci/93.24.1872

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