Nutrition Research and Practice

  • 제7권6호
  • /
  • Pages.439-445
  • /
  • 2013
  • /
  • 1976-1457(pISSN)
  • /
  • 2005-6168(eISSN)
한국영양학회 (The Korean Nutrition Society)
권호 표지
DOI QR코드

DOI QR Code

Anticarcinogenic effect of quercetin by inhibition of insulin-like growth factor (IGF)-1 signaling in mouse skin cancer

  • Jung, Minjeong (Department of Food Science and Nutrition, Kyungpook National University) ;
  • Bu, So Young (Department of Food and Nutrition, Daegu University) ;
  • Tak, Ka-Hee (Department of Food Science and Nutrition, Catholic University of Daegu) ;
  • Park, Jeong-Eun (Department of Food Science and Nutrition, Catholic University of Daegu) ;
  • Kim, Eunjung (Department of Food Science and Nutrition, Catholic University of Daegu)
  • 투고 : 2013.01.25
  • 심사 : 2013.07.26
  • 발행 : 2013.12.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

It has been shown that dysregulation of IGF-1 signaling is associated with tumor incidence and progression, whereas blockade of the signaling can effectively inhibit carcinogenesis. Although several mechanisms of anticancer activity of quercetin were proposed, molecular targets of quercetin have not been identified yet. Hence, we assessed the effect of quercetin on IGF-1 signaling inhibition in BK5.IGF-1 transgenic (Tg) mice, which over-expresses IGF-1 in the skin epidermis. A quercetin diet (0.02% wt/wt) for 20 weeks remarkably delayed the incidence of skin tumor by 2 weeks and reduced tumor multiplicity by 35% in a 7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two stage mouse skin carcinogenesis protocol. Moreover, skin hyperplasia in Tg mice was significantly inhibited by a quercetin supplementation. Further analysis of the MT1/2 skin papilloma cell line showed that a quercetin treatment dose dependently suppressed IGF-1 induced phosphorylation of the IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1, Akt and S6K; however, had no effect on the phosphorylation of PTEN. Additionally, the quercetin treatment inhibited IGF-1 stimulated cell proliferation in a dose dependent manner. Taken together, these data suggest that quercetin has a potent anticancer activity through the inhibition of IGF-1 signaling.

키워드

참고문헌

  1. Kim E, Goraksha-Hicks P, Li L, Neufeld TP, Guan KL. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol 2008;10:935-45. https://doi.org/10.1038/ncb1753
  2. Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, Rebholz H, Barnett J, Leslie NR, Cheng S, Shepherd PR, Gout I, Downes CP, Lamb RF. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol 2004;166:213-23. https://doi.org/10.1083/jcb.200403069
  3. Remacle-Bonnet MM, Garrouste FL, Heller S, André F, Marvaldi JL, Pommier GJ. Insulin-like growth factor-I protects colon cancer cells from death factor-induced apoptosis by potentiating tumor necrosis factor alpha-induced mitogen-activated protein kinase and nuclear factor kappaB signaling pathways. Cancer Res 2000;60: 2007-17.
  4. Shah OJ, Wang Z, Hunter T. Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr Biol 2004;14: 1650-6. https://doi.org/10.1016/j.cub.2004.08.026
  5. DiGiovanni J, Bol DK, Wilker E, Beltrán L, Carbajal S, Moats S, Ramirez A, Jorcano J, Kiguchi K. Constitutive expression of insulin-like growth factor-1 in epidermal basal cells of transgenic mice leads to spontaneous tumor promotion. Cancer Res 2000; 60:1561-70.
  6. Serafini M, Bellocco R, Wolk A, Ekström AM. Total antioxidant potential of fruit and vegetables and risk of gastric cancer. Gastroenterology 2002;123:985-91. https://doi.org/10.1053/gast.2002.35957
  7. Kyle JA, Sharp L, Little J, Duthie GG, McNeill G. Dietary flavonoid intake and colorectal cancer: a case-control study. Br J Nutr 2010;103:429-36. https://doi.org/10.1017/S0007114509991784
  8. Neuhouser ML. Dietary flavonoids and cancer risk: evidence from human population studies. Nutr Cancer 2004;50:1-7. https://doi.org/10.1207/s15327914nc5001_1
  9. Duthie SJ, Dobson VL. Dietary flavonoids protect human colonocyte DNA from oxidative attack in vitro. Eur J Nutr 1999;38:28-34. https://doi.org/10.1007/s003940050043
  10. Granado-Serrano AB, Martín MA, Bravo L, Goya L, Ramos S. Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2). J Nutr 2006;136:2715-21. https://doi.org/10.1093/jn/136.11.2715
  11. Phan TT, See P, Tran E, Nguyen TT, Chan SY, Lee ST, Huynh H. Suppression of insulin-like growth factor signalling pathway and collagen expression in keloid-derived fibroblasts by quercetin: its therapeutic potential use in the treatment and/or prevention of keloids. Br J Dermatol 2003;148:544-52. https://doi.org/10.1046/j.1365-2133.2003.05174.x
  12. Vijayababu MR, Kanagaraj P, Arunkumar A, Ilangovan R, Aruldhas MM, Arunakaran J. Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression. J Cancer Res Clin Oncol 2005;131:765-71. https://doi.org/10.1007/s00432-005-0005-4
  13. Senthilkumar K, Elumalai P, Arunkumar R, Banudevi S, Gunadharini ND, Sharmila G, Selvakumar K, Arunakaran J. Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Mol Cell Biochem 2010;344:173-84. https://doi.org/10.1007/s11010-010-0540-4
  14. Giuliani C, Noguchi Y, Harii N, Napolitano G, Tatone D, Bucci I, Piantelli M, Monaco F, Kohn LD. The flavonoid quercetin regulates growth and gene expression in rat FRTL-5 thyroid cells. Endocrinology 2008;149:84-92. https://doi.org/10.1210/en.2007-0618
  15. Murphy EA, Davis JM, McClellan JL, Carmichael MD. Quercetin's effects on intestinal polyp multiplicity and macrophage number in the Apc (Min/+) mouse. Nutr Cancer 2011;63:421-6. https://doi.org/10.1080/01635581.2011.535954
  16. Conti CJ, Fries JW, Viaje A, Miller DR, Morris R, Slaga TJ. In vivo behavior of murine epidermal cell lines derived from initiated and noninitiated skin. Cancer Res 1988;48:435-9.
  17. Satyamoorthy K, Li G, Vaidya B, Patel D, Herlyn M. Insulin-like growth factor-1 induces survival and growth of biologically early melanoma cells through both the mitogen-activated protein kinase and beta-catenin pathways. Cancer Res 2001;61:7318-24.
  18. Takeuchi K, Ito F. Receptor tyrosine kinases and targeted cancer therapeutics. Biol Pharm Bull 2011;34:1774-80. https://doi.org/10.1248/bpb.34.1774
  19. Gallagher EJ, LeRoith D. Minireview: IGF, insulin, and cancer. Endocrinology 2011;152:2546-51. https://doi.org/10.1210/en.2011-0231
  20. Vasanthi HR, Mukherjee S, Das DK. Potential health benefits of broccoli- a chemico-biological overview. Mini Rev Med Chem 2009;9:749-59. https://doi.org/10.2174/138955709788452685
  21. Slimestad R, Fossen T, Vagen IM. Onions: a source of unique dietary flavonoids. J Agric Food Chem 2007;55:10067-80. https://doi.org/10.1021/jf0712503
  22. Caltagirone S, Rossi C, Poggi A, Ranelletti FO, Natali PG, Brunetti M, Aiello FB, Piantelli M. Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int J Cancer 2000;87:595-600. https://doi.org/10.1002/1097-0215(20000815)87:4<595::AID-IJC21>3.0.CO;2-5
  23. Patel R, Krishnan R, Ramchandani A, Maru G. Polymeric black tea polyphenols inhibit mouse skin chemical carcinogenesis by decreasing cell proliferation. Cell Prolif 2008;41:532-53. https://doi.org/10.1111/j.1365-2184.2008.00528.x
  24. Lu G, Liao J, Yang G, Reuhl KR, Hao X, Yang CS. Inhibition of adenoma progression to adenocarcinoma in a 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine. Cancer Res 2006; 66:11494-501. https://doi.org/10.1158/0008-5472.CAN-06-1497
  25. Eming SA, Snow RG, Yarmush ML, Morgan JR. Targeted expression of insulin-like growth factor to human keratinocytes: modification of the autocrine control of keratinocyte proliferation. J Invest Dermatol 1996;107:113-20. https://doi.org/10.1111/1523-1747.ep12298351
  26. Werner H, Le Roith D. New concepts in regulation and function of the insulin-like growth factors: implications for understanding normal growth and neoplasia. Cell Mol Life Sci 2000;57:932-42. https://doi.org/10.1007/PL00000735
  27. Reiss K, Wang JY, Romano G, Furnari FB, Cavenee WK, Morrione A, Tu X, Baserga R. IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation. Oncogene 2000;19:2687-94. https://doi.org/10.1038/sj.onc.1203587
  28. Valentinis B, Romano G, Peruzzi F, Morrione A, Prisco M, Soddu S, Cristofanelli B, Sacchi A, Baserga R. Growth and differentiation signals by the insulin-like growth factor 1 receptor in hemopoietic cells are mediated through different pathways. J Biol Chem 1999;274:12423-30. https://doi.org/10.1074/jbc.274.18.12423
  29. Hyun T, Yam A, Pece S, Xie X, Zhang J, Miki T, Gutkind JS, Li W. Loss of PTEN expression leading to high Akt activation in human multiple myelomas. Blood 2000;96:3560-8.
  30. Cantley LC, Neel BG. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A 1999;96: 4240-5. https://doi.org/10.1073/pnas.96.8.4240
  31. Wang SI, Puc J, Li J, Bruce JN, Cairns P, Sidransky D, Parsons R. Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res 1997;57:4183-6.
  32. Erlund I, Freese R, Marniemi J, Hakala P, Alfthan G. Bioavailability of quercetin from berries and the diet. Nutr Cancer 2006; 54:13-7. https://doi.org/10.1207/s15327914nc5401_3
  33. Rupasinghe HP, Ronalds CM, Rathgeber B, Robinson RA. Absorption and tissue distribution of dietary quercetin and quercetin glycosides of apple skin in broiler chickens. J Sci Food Agric 2010;90:1172-8. https://doi.org/10.1002/jsfa.3944
  34. Koli R, Erlund I, Jula A, Marniemi J, Mattila P, Alfthan G. Bioavailability of various polyphenols from a diet containing moderate amounts of berries. J Agric Food Chem 2010;58:3927- https://doi.org/10.1021/jf9024823
  35. Santos MR, Rodriguez-Gomez MJ, Justino GC, Charro N, Florencio MH, Mira L. Influence of the metabolic profile on the in vivo antioxidant activity of quercetin under a low dosage oral regimen in rats. Br J Pharmacol 2008;153:1750-61. https://doi.org/10.1038/bjp.2008.46
  36. Agullo G, Gamet-Payrastre L, Manenti S, Viala C, Remesy C, Chap H, Payrastre B. Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: a comparison with tyrosine kinase and protein kinase C inhibition. Biochem Pharmacol 1997;53:1649-57. https://doi.org/10.1016/S0006-2952(97)82453-7
  37. Hagiwara M, Inoue S, Tanaka T, Nunoki K, Ito M, Hidaka H. Differential effects of flavonoids as inhibitors of tyrosine protein kinases and serine/threonine protein kinases. Biochem Pharmacol 1988;37:2987-92. https://doi.org/10.1016/0006-2952(88)90286-9
  38. Gamet-Payrastre L, Manenti S, Gratacap MP, Tulliez J, Chap H, Payrastre B. Flavonoids and the inhibition of PKC and PI 3-kinase. Gen Pharmacol 1999;32:279-86. https://doi.org/10.1016/S0306-3623(98)00220-1
  39. Yoshizumi M, Tsuchiya K, Kirima K, Kyaw M, Suzaki Y, Tamaki T. Quercetin inhibits Shc- and phosphatidylinositol 3- kinase-mediated c-Jun N-terminal kinase activation by angiotensin II in cultured rat aortic smooth muscle cells. Mol Pharmacol 2001;60:656-65.
  40. Ranelletti FO, Ricci R, Larocca LM, Maggiano N, Capelli A, Scambia G, Benedetti-Panici P, Mancuso S, Rumi C, Piantelli M. Growth-inhibitory effect of quercetin and presence of type-II estrogen-binding sites in human colon-cancer cell lines and primary colorectal tumors. Int J Cancer 1992;50:486-92. https://doi.org/10.1002/ijc.2910500326
  41. Ashida H, Fukuda I, Yamashita T, Kanazawa K. Flavones and flavonols at dietary levels inhibit a transformation of aryl hydrocarbon receptor induced by dioxin. FEBS Lett 2000;476:213-7. https://doi.org/10.1016/S0014-5793(00)01730-0

피인용 문헌

  1. Review of Natural Compounds for Potential Skin Cancer Treatment vol.19, pp.8, 2014, https://doi.org/10.3390/molecules190811679
  2. Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: Promising options for prevention and treatment of uterine fibroids? vol.58, pp.8, 2014, https://doi.org/10.1002/mnfr.201400134
  3. Antimicrobial Dyeing of Cotton and Silk Fabrics Using Houttuynia cordata Extract vol.27, pp.3, 2015, https://doi.org/10.5764/TCF.2015.27.3.194
  4. Quercetin: A Promising Flavonoid with a Dynamic Ability to Treat Various Diseases, Infections, and Cancers vol.07, pp.02, 2016, https://doi.org/10.4236/jct.2016.72010
  5. vol.120, pp.4, 2016, https://doi.org/10.1111/jam.13073
  6. Anticancer potential of quercetin: A comprehensive review pp.0951418X, 2018, https://doi.org/10.1002/ptr.6155
  7. Insulin-Like Growth Factor System in Cancer: Novel Targeted Therapies vol.2015, pp.None, 2013, https://doi.org/10.1155/2015/538019
  8. Therapeutic Targeting of the IGF Axis vol.8, pp.8, 2019, https://doi.org/10.3390/cells8080895
  9. Evidence that peroxisome proliferator‐activated receptor γ suppresses squamous carcinogenesis through anti‐inflammatory signaling and regulation of the immune response vol.58, pp.9, 2019, https://doi.org/10.1002/mc.23041
  10. Aldehyde oxidase at the crossroad of metabolism and preclinical screening vol.51, pp.4, 2013, https://doi.org/10.1080/03602532.2019.1667379
  11. Quercetin–Resveratrol Combination for Prostate Cancer Management in TRAMP Mice vol.12, pp.8, 2013, https://doi.org/10.3390/cancers12082141
  12. Characteristics and Dyeability of Distilled Water and Ethanol Extracts of Houttuynia cordata vol.29, pp.6, 2013, https://doi.org/10.5934/kjhe.2020.29.6.931
  13. The therapeutic effects of blocking IGF-R1 on mice model of skin cancer vol.32, pp.7, 2013, https://doi.org/10.1080/09546634.2019.1708243