MORIN PREVENTS ULTRAVIOLET-B RADIATION-INDUCED PHOTOCARCINOGENESIS THROUGH ACTIVATING THROMBOSPONDIN-1 IN THE MOUSE SKIN
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i3.21652Keywords:
Ultraviolet B radiation, Morin, Photocarcinogenesis, Thrombospondin-1Abstract
 Objective: In this study, we investigated whether morin, a natural flavonoid, could able to inhibit ultraviolet B (UVB)-induced carcinogenesis in the skin of Swiss albino mice.
Methods: The mice were exposed to UVB radiation (180 mJ/cm2) on weekly thrice for 30 weeks, and morin was administered intraperitoneal and topical application 1 h before UVB exposure. UVB radiation induces the overexpression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and Bcl-2 genes.
Results: Morin significantly prevented UVB-induced activation of COX-2, iNOS, VEGF, TGF-β, and Bcl-2 expression in mouse skin. Thrombospondin-1 (TSP), a novel endogenous factor, inhibits angiogenesis and inflammation.
Conclusion: The present study illustrates that the protective effect of morin against UVB-induced carcinogenesis may be modulated through activation of TSP-1 in UVB-exposed Swiss albino mice.
Downloads
References
WHO. Ultraviolet Radiation and the Intersun Programme Report; 2012. Available from: http://www.who.int/uv/health/en.
Anitha T. Medicinal plants used in skin protection. Asian J Pharm Clin Res 2012;5:35-8.
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: How are they linked? Free Radic Biol Med 2010;49:1603-16.
Trompezinski S, Pernet I, Schmitt D, Viac J. UV radiation and prostaglandin E2 up-regulate vascular endothelial growth factor (VEGF) in cultured human fibroblasts. Inflamm Res 2001;50:422-7.
Jung SK, Lee KW, Byun S, Lee EJ, Kim JE, Bode AM, et al. Myricetin inhibits UVB-induced angiogenesis by regulating PI-3 kinase in vivo. Carcinogenesis 2010;31:911-7.
Jeanne A, Schneider C, Martiny L, Dedieu S. Original insights on thrombospondin-1-related antireceptor strategies in cancer. Front Pharmacol 2015;6:252.
Kazerounian S, Yee KO, Lawler J. Thrombospondins in cancer. Cell Mol Life Sci 2008;65:700-12.
Tong X, Mirzoeva S, Veliceasa D, Bridgeman BB, Fitchev P, Cornwell ML, et al. Chemopreventive apigenin controls UVB-induced cutaneous proliferation and angiogenesis through huR and thrombospondin-1. Oncotarget 2014;5:11413-27.
Lee CH, Wu SB, Hong CH, Yu HS, Wei YH. Molecular mechanisms of UV-induced apoptosis and its effects on skin residential cells: The implication in UV-based phototherapy. Int J Mol Sci 2013;14:6414-35.
Zamzami N, Marchetti P, Castedo M, Zanin C, Vayssière JL, Petit PX, et al. Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J Exp Med 1995;181:1661-72.
Jyoti BC, Balaji KS, Jayarama S, Wethroe K. Evaluation of apoptogenic effects of Averrhoa bilambi extract on enrlich ascites carcinoma bearing mice. Asian J Pharm Clin Res 2016;9:348-52.
Korać RR, Khambholja KM. Potential of herbs in skin protection from ultraviolet radiation. Pharmacogn Rev 2011;5:164.
krishnan KP, Narayanaswamy N. Botanicals as sunscreens: Their role in the prevention of photoaging and skin cancer. Int J Res Cos Sci 2011;1:1-2.
Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2009;2:270-8.
Nandhakumar R, Salini K, Devaraj SN. Morin augments anticarcinogenic and antiproliferative efficacy against 7, 12-dimethylbenz (a)-anthracene induced experimental mammary carcinogenesis. Mol Cell Biochem 2012;364:79-92.
Prahalathan P, Kumar S, Raja B. Morin attenuates blood pressure and oxidative stress in deoxycorticosterone acetate-salt hypertensive rats: A biochemical and histopathological evaluation. Metabolism 2012;61:1087-99.
Merwid-Ląd A, Trocha M, Chlebda E, Sozański T, Magdalan J, Ksiądzyna D, et al. Effects of morin-5′-sulfonic acid sodium salt (NaMSA) on cyclophosphamide-induced changes in oxido-redox state in rat liver and kidney. Hum Exp Toxicol 2012;31:812-9.
Fang SH, Hou YC, Chang WC, Hsiu SL, Chao PD, Chiang BL, et al. Morin sulfates/glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock. Life Sci 2003;74:743-56.
Lee MH, Cha HJ, Choi EO, Han MH, Kim SO, Kim GY et al. Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2 mediated HO-1 expression in V79-4 Chinese hamster lung fibroblasts. Int J Mol Med. 2017;39:672-680.
Kok LD, Wong YP, Wu TW, Chan HC, Kwok TT, Fung KP, et al. Morin hydrate: A potential antioxidant in minimizing the free-radicals-mediated damage to cardiovascular cells by anti-tumor drugs. Life Sci 2000;67:91-9.
Kuo HM, Chang LS, Lin YL, Lu HF, Yang JS, Lee JH, et al. Morin inhibits the growth of human leukemia HL-60 cells via cell cycle arrest and induction of apoptosis through mitochondria dependent pathway. Anticancer Res 2007;27:395-405.
Vaid M, Katiyar SK. Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn.) (Review). Int J Oncol 2010;36:1053-60.
Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc Natl Acad Sci U S A 1979;76:4350-4.
Schrodinger Suite. The Induced Fit Docking Protocol. New York, NY: Schrodinger, LLC; 2009.
Induced Fit Docking Protocol. Glide, Version 5.5. New York, NY: Schrodinger, LLC; 2009.
Lee EH, Faulhaber D, Hanson KM, Ding W, Peters S, Kodali S, et al. Dietary lutein reduces ultraviolet radiation-induced inflammation and immunosuppression. J Invest Dermatol 2004;122:510-7.
Rice-Evans C, Miller N, Paganga G. Antioxidant properties of phenolic compounds. J Invest Dermatol 1997;2:152-9.
Dai J, Mumper RJ. Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules 2010;15:7313-52.
Dzialo M, Mierziak J, Korzun U, Preisner M, Szopa J, Kulma A. The Potential of Plant Phenolics in Prevention and Therapy of Skin Disorders. Int J Mol Sci. 2016;17:160.
Lin FH, Lin JY, Gupta RD, Tournas JA, Burch JA, Selim MA, et al. Ferulic acid stabilizes a solution of vitamins C and E and doubles its photo protection of skin. J Invest Dermatol 2005;125;826-32.
Meeran SM, Punathil T, Katiyar SK. IL-12 deficiency exacerbates inflammatory responses in UV-irradiated skin and skin tumors. J Invest Dermatol 2008;128:2716-27.
Cheng W, Li J, You T, Hu C. Anti-inflammatory and immunomodulatory activities of the extracts from the inflorescence of Chrysanthemum indicum Linne. J Ethnopharmacol 2005;101:334-7.
Liedtke AJ, Crews BC, Daniel CM, Blobaum AL, Kingsley PJ, Ghebreselasie K, et al. Cyclooxygenase-1-selective inhibitors based on the (E)-2′-des-methyl-sulindac sulfide scaffold. J Med Chem 2012;55:2287-300.
Bates DO. Vascular endothelial growth factors and vascular permeability. Cardiovasc Res 2010;87:262-71.
Balupillai A, Prasad RN, Ramasamy K, Muthusamy G, Shanmugham M, Govindasamy K, et al. Caffeic acid inhibits UVB-induced inflammation and photocarcinogenesis through activation of peroxisome proliferator-activated receptor-γ in mouse skin. Photochem Photobiol 2015;91:1458-68.
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA, et al. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 2004;56:549-80.
Santibanez JF. Transforming growth factor-Beta and urokinase-type plasminogen activator: Dangerous partners in tumorigenesis-implications in skin cancer. ISRN Dermatol 2013;2013:597927.
Glick AB. TGF? Back to the future: Revisiting its role as a transforming growth factor. Canc Biol Ther 2004;3:276-83.
Yano K, Kadoya K, Kajiya K, Hong YK, Detmar M. Ultraviolet B irradiation of human skin induces an angiogenic switch that is mediated by up regulation of vascular endothelial growth factor and by down regulation of thrombospondin-1. Br J Dermatol 2005;152:115-21.
Kim KH, Back JH, Zhu Y, Arbesman J, Athar M, Kopelovich L, et al. Resveratrol targets transforming growth factor-β2 signaling to block UV-induced tumor progression. J Invest Dermatol 2011;131:195-202.
Ambothi K, Prasad NR, Balupillai A. Ferulic acid inhibits UVB-radiation induced photo carcinogenesis through modulating inflammatory and apoptotic signaling in swiss albino mice. Food Chem Toxicol 2015;82:72-8.
Miyata Y, Sakai H. Thrombospondin-1 in urological cancer: Pathological role, clinical significance, and therapeutic prospects. Int J Mol Sci 2013;14:12249-72.
Reagan-Shaw S, Breur J, Ahmad N. Enhancement of UVB radiation–mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes. Mol Canc Ther 2006;5:418-29.
Frenzel A, Grespi F, Chmelewskij W, Villunger A. Bcl2 family proteins in carcinogenesis and the treatment of cancer. Apoptosis 2009;14:584-96.
Plati J, Bucur O, Khosravi-Far R. Apoptotic cell signaling in cancer progression and therapy. Integr Biol (Camb) 2011;3:279-96.
Park C, Lee WS, Go SI, Nagappan A, Han MH, Hong SH, et al. Morin, a flavonoid from moraceae, induces apoptosis by induction of BAD protein in human leukemic cells. Int J Mol Sci 2014;16:645-59.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
