Please use this identifier to cite or link to this item:
標題: The Antioxidant Capacity of Different Cultivars and Maturities of Mulberry and the Antimetastatic Potential of 1-Deoxynojirimycin on B16F10 cells via Its Direct Inhibitory Effect and Immune-Enhancing Effect
作者: Wang, Ran-Juh
關鍵字: mulberry;抗氧化能力;antioxidant capacity;principal component analysis;1-deoxynojirimycin;metastasis;matrix metalloproteinases;tissue inhibitors of metalloproteinase;immunomodulatory;主成份分析;1-脫氧氮雜-D-葡萄糖;轉移;基質金屬蛋白酶組織金屬蛋白酶抑制劑;免疫調節
出版社: 食品暨應用生物科技學系所
引用: 1. Chang, J.C. 2008. ''Miaoli No. 1'' mulberry: a new cultivar for berry production. HortScience 43:1594-1595. 2. Liu, L.K., H.J. Lee, Y.W. Shih, C.C. Chyau, and C.J. Wang. 2008. Mulberry anthocyanin extracts inhibit LDL oxidation and macrophage-derived foam cell formation induced by oxidative LDL. J Food Sci 73:H113-121. 3. Liu, L.K., F.P. Chou, Y.C. Chen, C.C. Chyau, H.H. Ho, and C.J. Wang. 2009. Effects of mulberry (Morus alba L.) extracts on lipid homeostasis in vitro and in vivo. J Agric Food Chem 57:7605-7611. 4. Nakagawa, K., H. Kubota, T. Kimura, S. Yamashita, T. Tsuzuki, S. Oikawa, and T. Miyazawa. 2007. Occurrence of orally administered mulberry 1-deoxynojirimycin in rat plasma. J Agric Food Chem 55:8928-8933. 5. Andallu, B., and N.C. Varadacharyulu. 2007. Gluconeogenic substrates and hepatic gluconeogenic enzymes in streptozotocin-diabetic rats: effect of mulberry (Morus indica L.) leaves. J Med Food 10:41-48. 6. Hu, M.L., and R.J. Wang. 2004. Antioxidant role of mulberry leaves in streptozotocin-diabetic rats. Clin Chim Acta 348:215; author reply 217-218. 7. Andallu, B., and N. Varadacharyulu. 2003. Antioxidant role of mulberry (Morus indica L. cv. Anantha) leaves in streptozotocin-diabetic rats. Clin Chim Acta 338:3-10. 8. Andallu, B., V. Suryakantham, B. Lakshmi Srikanthi, and G.K. Reddy. 2001. Effect of mulberry (Morus indica L.) therapy on plasma and erythrocyte membrane lipids in patients with type 2 diabetes. Clin Chim Acta 314:47-53. 9. Huang, H.P., Y.W. Shih, Y.C. Chang, C.N. Hung, and C.J. Wang. 2008. Chemoinhibitory effect of mulberry anthocyanins on melanoma metastasis involved in the Ras/PI3K pathway. J Agric Food Chem 56:9286-9293. 10. Chen, P.N., S.C. Chu, H.L. Chiou, W.H. Kuo, C.L. Chiang, and Y.S. Hsieh. 2006. Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. Cancer Lett. 235:248-259. 11. Lin, J.Y., and C.Y. Tang. 2007. Determination of total phenolic and flavonoid contents in selected fruits and vegetables, as well as their stimulatory effects on mouse splenocyte proliferation. Food Chem 101:140-147. 12. Kang, T.H., H.R. Oh, S.M. Jung, J.H. Ryu, M.W. Park, Y.K. Park, and S.Y. Kim. 2006. Enhancement of neuroprotection of mulberry leaves (Morus alba L.) prepared by the anaerobic treatment against ischemic damage. Biol Pharm Bull 29:270-274. 13. Kim, J.Y., H.J. Kwon, J.Y. Jung, H.Y. Kwon, J.G. Baek, Y.S. Kim, and O. Kwon. 2010. Comparison of absorption of 1-deoxynojirimycin from mulberry water extract in rats. J Agric Food Chem 58:6666-6671. 14. Song, W., H.J. Wang, P. Bucheli, P.F. Zhang, D.Z. Wei, and Y.H. Lu. 2009. Phytochemical profiles of different mulberry (Morus sp.) species from China. J Agric Food Chem 57:9133-9140. 15. Seifried, H.E., D.E. Anderson, E.I. Fisher, and J.A. Milner. 2007. A review of the interaction among dietary antioxidants and reactive oxygen species. J. Nutr. Biochem. 18:567-579. 16. Kulkarni, A.P., S.M. Aradhya, and S. Divakar. 2004. Isolation and identification of a radical scavenging antioxidant - punicalagin from pith and carpellary membrane of pomegranate fruit. Food Chem 87:551-557. 17. Wang, S.Y., and H.S. Lin. 2000. Antioxidant activity in fruits and leaves of blackberry, raspberry, and strawberry varies with cultivar and developmental stage. J Agric Food Chem 48:140-146. 18. Zheng, W., and S.Y. Wang. 2003. Oxygen radical absorbing capacity of phenolics in blueberries, cranberries, chokeberries, and lingonberries. J Agric Food Chem 51:502-509. 19. Huang, R., R. Xia, L. Hu, Y. Lu, and M. Wang. 2007. Antioxidant activity and oxygen-scavenging system in orange pulp during fruit ripening and maturation. Sci. Hortic. 113:166-172. 20. Guo, C., J. Yang, J. Wei, Y. Li, J. Xu, and Y. Jiang. 2003. Antioxidant activities of peel, pulp and seed fractions of common fruits as determined by FRAP assay. Nutr Res 23:1719-1726. 21. Mahattanatawee, K., J.A. Manthey, G. Luzio, S.T. Talcott, K. Goodner, and E.A. Baldwin. 2006. Total antioxidant activity and fiber content of select Florida-grown tropical fruits. J Agric Food Chem 54:7355-7363. 22. Prior, R.L., X. Wu, and K. Schaich. 2005. Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements. J Agric Food Chem 53:4290-4302. 23. Ronis, M.J.J., A. Butura, B.P. Sampey, K. Shankar, R.L. Prior, S. Korourian, E. Albano, M. Ingelman-Sundberg, D.R. Petersen, and T.M. Badger. 2005. Effects of N-acetylcysteine on ethanol-induced hepatotoxicity in rats fed via total enteral nutrition. Free Radic. Biol. Med. 39:619-630. 24. Aruoma, O.I. 2003. Methodological considerations for characterizing potential antioxidant actions of bioactive components in plant foods. Mutat. Res. 523-524:9-20. 25. Dudjak, L.A. 1992. Cancer metastasis. Semin Oncol Nurs 8:40-50. 26. Bohle, A.S., and H. Kalthoff. 1999. Molecular mechanisms of tumor metastasis and angiogenesis. Langenbecks Arch Surg 384:133-140. 27. Westermarck, J., and V.M. Kahari. 1999. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 13:781-792. 28. Hofmann, U.B., J.R. Westphal, G.N. Van Muijen, and D.J. Ruiter. 2000. Matrix metalloproteinases in human melanoma. J Invest Dermatol 115:337-344. 29. Hofmann, U.B., A.A. Eggert, K. Blass, E.B. Brocker, and J.C. Becker. 2003. Expression of matrix metalloproteinases in the microenvironment of spontaneous and experimental melanoma metastases reflects the requirements for tumor formation. Cancer Res 63:8221-8225. 30. Gohji, K., N. Fujimoto, A. Fujii, T. Komiyama, J. Okawa, and M. Nakajima. 1996. Prognostic significance of circulating matrix metalloproteinase-2 to tissue inhibitor of metalloproteinases-2 ratio in recurrence of urothelial cancer after complete resection. Cancer Res 56:3196-3198. 31. El-Shabrawi, Y., N. Ardjomand, and H. Radner. 2001. MMP-9 is predominantly expressed in epithelioid and not spindle cell uveal melanoma. J Pathol 194:201-206. 32. Kimura, T., K. Nakagawa, Y. Saito, K. Yamagishi, M. Suzuki, K. Yamaki, H. Shinmoto, and T. Miyazawa. 2004. Determination of 1-deoxynojirimycin in mulberry leaves using hydrophilic interaction chromatography with evaporative light scattering detection. J Agric Food Chem 52:1415-1418. 33. Nakagawa, K., H. Kubota, T. Kimura, S. Yamashita, T. Tsuzuki, S. Oikawa, and T. Miyazawa. 2007. Occurrence of orally administered mulberry 1-deoxynojirimycin in rat plasma. J Agric Food Chem 55:8928-8933. 34. Humphries, M.J., K. Matsumoto, S.L. White, and K. Olden. 1986. Inhibition of experimental metastasis by castanospermine in mice: blockage of two distinct stages of tumor colonization by oligosaccharide processing inhibitors. Cancer Res 46:5215-5222. 35. Spearman, M.A., J.E. Damen, T. Kolodka, A.H. Greenberg, J.C. Jamieson, and J.A. Wright. 1991. Differential effects of glycoprotein processing inhibition on experimental metastasis formation by T24-H-ras transformed fibroblasts. Cancer Lett 57:7-13. 36. Seftor, R.E., E.A. Seftor, W.J. Grimes, L.A. Liotta, W.G. Stetler-Stevenson, D.R. Welch, and M.J. Hendrix. 1991. Human melanoma cell invasion is inhibited in vitro by swainsonine and deoxymannojirimycin with a concomitant decrease in collagenase IV expression. Melanoma Res 1:43-54. 37. Nakagawa, K., K. Ogawa, O. Higuchi, T. Kimura, T. Miyazawa, and M. Hori. 2010. Determination of iminosugars in mulberry leaves and silkworms using hydrophilic interaction chromatography-tandem mass spectrometry. Anal Biochem 404:217-222. 38. Tsuruoka, T., H. Fukuyasu, M. Ishii, T. Usui, S. Shibahara, and S. Inouye. 1996. Inhibition of mouse tumor metastasis with nojirimycin-related compounds. J Antibiot (Tokyo) 49:155-161. 39. Flanagan, J.J., B. Rossi, K. Tang, X. Wu, K. Mascioli, F. Donaudy, M.R. Tuzzi, F. Fontana, M.V. Cubellis, C. Porto, E. Benjamin, D.J. Lockhart, K.J. Valenzano, G. Andria, G. Parenti, and H.V. Do. 2009. The pharmacological chaperone 1-deoxynojirimycin increases the activity and lysosomal trafficking of multiple mutant forms of acid alpha-glucosidase. Hum Mutat 30:1683-1692. 40. Kimura, T., K. Nakagawa, H. Kubota, Y. Kojima, Y. Goto, K. Yamagishi, S. Oita, S. Oikawa, and T. Miyazawa. 2007. Food-grade mulberry powder enriched with 1-deoxynojirimycin suppresses the elevation of postprandial blood glucose in humans. J Agric Food Chem 55:5869-5874. 41. Kong, W.H., S.H. Oh, Y.R. Ahn, K.W. Kim, J.H. Kim, and S.W. Seo. 2008. Antiobesity effects and improvement of insulin sensitivity by 1-deoxynojirimycin in animal models. J Agric Food Chem 56:2613-2619. 42. Voss, A.A., A. Diez-Sampedro, B.A. Hirayama, D.D. Loo, and E.M. Wright. 2007. Imino sugars are potent agonists of the human glucose sensor SGLT3. Mol Pharmacol 71:628-634. 43. Nakagawa, K., H. Kubota, T. Tsuzuki, J. Kariya, T. Kimura, S. Oikawa, and T. Miyazawa. 2008. Validation of an ion trap tandem mass spectrometric analysis of mulberry 1-deoxynojirimycin in human plasma: application to pharmacokinetic studies. Biosci Biotechnol Biochem 72:2210-2213. 44. Tsuduki, T., Y. Nakamura, T. Honma, K. Nakagawa, T. Kimura, I. Ikeda, and T. Miyazawa. 2009. Intake of 1-deoxynojirimycin suppresses lipid accumulation through activation of the beta-oxidation system in rat liver. J Agric Food Chem 57:11024-11029. 45. Atsumi, S., C. Nosaka, Y. Ochi, H. Iinuma, and K. Umezawa. 1993. Inhibition of experimental metastasis by an a-glucosidase inhibitor, 1,6-epi-cyclophellitol. Cancer Res 53:4896-4899. 46. Goss, P.E., C.L. Reid, D. Bailey, and J.W. Dennis. 1997. Phase IB clinical trial of the oligosaccharide processing inhibitor swainsonine in patients with advanced malignancies. Clin Cancer Res 3:1077-1086. 47. Guerrera, M., and S. Ladisch. 2003. N-butyldeoxynojirimycin inhibits murine melanoma cell ganglioside metabolism and delays tumor onset. Cancer Lett 201:31-40. 48. Drake, P.M., W. Cho, B. Li, A. Prakobphol, E. Johansen, N.L. Anderson, F.E. Regnier, B.W. Gibson, and S.J. Fisher. 2010. Sweetening the pot: adding glycosylation to the biomarker discovery equation. Clin Chem 56:223-236. 49. Nakahara, S., and A. Raz. 2008. Biological modulation by lectins and their ligands in tumor progression and metastasis. Anticancer Agents Med Chem 8:22-36. 50. Chang, W.W., C.Y. Yu, T.W. Lin, P.H. Wang, and Y.C. Tsai. 2006. Soyasaponin I decreases the expression of a-2,3-linked sialic acid on the cell surface and suppresses the metastatic potential of B16F10 melanoma cells. Biochem Biophys Res Commun 341:614-619. 51. Reddy, B.V., and R.D. Kalraiya. 2006. Sialilated b-1,6 branched N-oligosaccharides modulate adhesion, chemotaxis and motility of melanoma cells: Effect on invasion and spontaneous metastasis properties. Biochim Biophys Acta 1760:1393-1402. 52. Yu, J., R. Tian, B. Xiu, J. Yan, R. Jia, L. Zhang, A.E. Chang, H. Song, and Q. Li. 2009. Antitumor activity of T cells generated from lymph nodes draining the SEA-expressing murine B16 melanoma and secondarily activated with dendritic cells. Int J Biol Sci 5:135-146. 53. Vyavahare, V.P., C. Chakraborty, B. Maity, S. Chattopadhyay, V.G. Puranik, and D.D. Dhavale. 2007. Synthesis of 1-deoxy-1-hydroxymethyl- and 1-deoxy-1-epi-hydroxymethyl castanospermine as new potential immunomodulating agents. J Med Chem 50:5519-5523. 54. Voshol, H., H.F. Dullens, W. Den Otter, and J.F. Vliegenthart. 1996. The glycosylation profile of interleukin-2 activated human lymphocytes correlates to their anti-tumor activity. Anticancer Res 16:155-159. 55. Voshol, H., H.F. Dullens, W. Den Otter, and J.F. Vliegenthart. 1993. Cell surface glycoconjugates as possible target structures for human natural killer cells: evidence against the involvement of glycolipids and N-linked carbohydrate chains. Glycobiology 3:69-76. 56. White, S.L., K. Schweitzer, M.J. Humphries, and K. Olden. 1988. Stimulation of DNA synthesis in murine lymphocytes by the drug swainsonine: immunomodulatory properties. Biochem Biophys Res Commun 150:615-625. 57. Humphries, M.J., K. Matsumoto, S.L. White, R.J. Molyneux, and K. Olden. 1988. Augmentation of murine natural killer cell activity by swainsonine, a new antimetastatic immunomodulator. Cancer Res 48:1410-1415. 58. Newton, S.A., S.L. White, M.J. Humphries, and K. Olden. 1989. Swainsonine inhibition of spontaneous metastasis. J Natl Cancer Inst 81:1024-1028. 59. Peyrieras, N., E. Bause, G. Legler, R. Vasilov, L. Claesson, P. Peterson, and H. Ploegh. 1983. Effects of the glucosidase inhibitors nojirimycin and deoxynojirimycin on the biosynthesis of membrane and secretory glycoproteins. EMBO J 2:823-832. 60. Mohla, S., M.J. Humphries, S.L. White, K. Matsumoto, S.A. Newton, C.C. Sampson, D. Bowen, and K. Olden. 1989. Swainsonine: a new antineoplastic immunomodulator. J Natl Med Assoc 81:1049-1056. 61. Wang, H., G. Cao, and R.L. Prior. 1996. Total antioxidant capacity of fruits. J Agric Food Chem 44:701-705. 62. Zafra-Stone, S., T. Yasmin, M. Bagchi, A. Chatterjee, J.A. Vinson, and D. Bagchi. 2007. Berry anthocyanins as novel antioxidants in human health and disease prevention. Mol Nutr Food Res 51:675-683. 63. Naderi, G., S. Asgary, N. Sarraf-Zadegan, H. Oroojy, and F. Afshin-Nia. 2004. Antioxidant activity of three extracts of Morus nigra. Phytother Res 18:365-369. 64. Heinonen, I.M., A.S. Meyer, and E.N. Frankel. 1998. Antioxidant activity of berry phenolics on human low-density lipoprotein and liposome oxidation. J Agric Food Chem 46:4107-4112. 65. Ogawa, K., H. Sakakibara, R. Iwata, T. Ishii, T. Sato, T. Goda, K. Shimoi, and S. Kumazawa. 2008. Anthocyanin composition and antioxidant activity of the crowberry (Empetrum nigrum) and other berries. J Agric Food Chem 56:4457-4462. 66. Ou, B., D. Huang, M. Hampsch-Woodill, J.A. Flanagan, and E.K. Deemer. 2002. Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: a comparative study. J Agric Food Chem 50:3122-3128. 67. Çam, M., Y. HisIl, and G. Durmaz. 2009. Classification of eight pomegranate juices based on antioxidant capacity measured by four methods. Food Chem 112:721-726. 68. Cao, G., H.M. Alessio, and R.G. Cutler. 1993. Oxygen-radical absorbance capacity assay for antioxidants. Free Radic. Biol. Med. 14:303-311. 69. Bae, S.H., and H.J. Suh. 2007. Antioxidant activities of five different mulberry cultivars in Korea. LWT 40:955-962. 70. Ercisli, S., and E. Orhan. 2008. Some physico-chemical characteristics of black mulberry (Morus nigra L.) genotypes from Northeast Anatolia region of Turkey. Sci. Hortic. 116:41-46. 71. Gungor, N., and M. Sengul. 2008. Antioxidant activity, total phenolic content and selected physicochemical properties of white mulberry (Morus alba L.) fruits. Int. J. Food Prop. 11:44-52. 72. Prior, R.L., G. Cao, A. Martin, E. Sofic, J. McEwen, C. O''Brien, N. Lischner, M. Ehlenfeldt, W. Kalt, G. Krewer, and C.M. Mainland. 1998. Antioxidant capacity as influenced by total phenolic and anthocyanin content, maturity, and variety of Vaccinium species. J Agric Food Chem 46:2686-2693. 73. Özgen, M., S. Serçe, and C. Kaya. 2009. Phytochemical and antioxidant properties of anthocyanin-rich Morus nigra and Morus rubra fruits. Scientia Horticulturae 119:275-279. 74. Reyes-Carmona, J., G.G. Yousef, R.A. Martinez-Peniche, and M.A. Lila. 2005. Antioxidant capacity of fruit extracts of blackberry (Rubus sp.) produced in different climatic regions. J. Food Sci. 70:S497-S503. 75. Aaby, K., G. Skrede, and R.E. Wrolstad. 2005. Phenolic composition and antioxidant activities in flesh and achenes of strawberries (Fragaria ananassa). J Agric Food Chem 53:4032-4040. 76. Wong, S.P., L.P. Leong, and J.H.W. Koh. 2006. Antioxidant activities of aqueous extracts of selected plants. Food Chem 99:775-783. 77. Yamazaki, D., S. Kurisu, and T. Takenawa. 2005. Regulation of cancer cell motility through actin reorganization. Cancer Sci 96:379-386. 78. Hedlund, M., E. Ng, A. Varki, and N.M. Varki. 2008. a-2,6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo. Cancer Res 68:388-394. 79. Dennis, J.W., and S. Laferte. 1987. Tumor cell surface carbohydrate and the metastatic phenotype. Cancer Metastasis Rev 5:185-204. 80. Cao, Y., A. Merling, P.R. Crocker, R. Keller, and R. Schwartz-Albiez. 2002. Differential expression of b-galactoside a-2,6 sialyltransferase and sialoglycans in normal and cirrhotic liver and hepatocellular carcinoma. Lab Invest 82:1515-1524. 81. Mellor, H.R., D.C. Neville, D.J. Harvey, F.M. Platt, R.A. Dwek, and T.D. Butters. 2004. Cellular effects of deoxynojirimycin analogues: inhibition of N-linked oligosaccharide processing and generation of free glucosylated oligosaccharides. Biochem J 381:867-875. 82. Clark, I.M., T.E. Swingler, C.L. Sampieri, and D.R. Edwards. 2008. The regulation of matrix metalloproteinases and their inhibitors. Int J Biochem Cell Biol 40:1362-1378. 83. Sampieri, C.L., R.K. Nuttall, D.A. Young, D. Goldspink, I.M. Clark, and D.R. Edwards. 2008. Activation of p38 and JNK MAPK pathways abrogates requirement for new protein synthesis for phorbol ester mediated induction of select MMP and TIMP genes. Matrix Biol 27:128-138. 84. Khokha, R., P. Waterhouse, S. Yagel, P.K. Lala, C.M. Overall, G. Norton, and D.T. Denhardt. 1989. Antisense RNA-induced reduction in murine TIMP levels confers oncogenicity on Swiss 3T3 cells. Science 243:947-950. 85. Ray, S., N. Chattopadhyay, N. Biswas, and A. Chatterjee. 1999. Regulatory molecules in tumor metastasis. J Environ Pathol Toxicol Oncol 18:251-259. 86. Khokha, R. 1994. Suppression of the tumorigenic and metastatic abilities of murine B16-F10 melanoma cells in vivo by the overexpression of the tissue inhibitor of the metalloproteinases-1. J Natl Cancer Inst 86:299-304. 87. Olden, K., S. Mohla, S.A. Newton, S.L. White, and M.J. Humphries. 1988. Use of antiadhesive peptide and swainsonine to inhibit metastasis. Ann N Y Acad Sci 551:421-442. 88. Olden, K., S.A. Newton, T. Nagai, Y. Yasuda, K. Grzegorzewski, P. Breton, O. Oredipe, and S.L. White. 1992. The use of novel antineoplastic agents to inhibit the growth and metastasis of malignant melanoma and other cancers. Pigment Cell Res Suppl 2:219-233. 89. Elbein, A.D. 1991. Glycosidase inhibitors: inhibitors of N-linked oligosaccharide processing. FASEB J 5:3055-3063. 90. Zhou, Y., Y. Zhao, K.M. O''Boyle, and P.V. Murphy. 2008. Hybrid angiogenesis inhibitors: synthesis and biological evaluation of bifunctional compounds based on 1-deoxynojirimycin and aryl-1,2,3-triazoles. Bioorg Med Chem Lett 18:954-958. 91. Goss, P.E., J. Baptiste, B. Fernandes, M. Baker, and J.W. Dennis. 1994. A phase I study of swainsonine in patients with advanced malignancies. Cancer Res 54:1450-1457. 92. Nishimura, Y. 2003. gem-Diamine 1-N-iminosugars and related iminosugars, candidate of therapeutic agents for tumor metastasis. Curr Top Med Chem 3:575-591. 93. Sun, J.Y., M.Z. Zhu, S.W. Wang, S. Miao, Y.H. Xie, and J.B. Wang. 2007. Inhibition of the growth of human gastric carcinoma in vivo and in vitro by swainsonine. Phytomedicine 14:353-359. 94. Mukherjee, P., A.C. Faber, L.M. Shelton, R.C. Baek, T.C. Chiles, and T.N. Seyfried. 2008. Ganglioside GM3 suppresses the pro-angiogenic effects of vascular endothelial growth factor and ganglioside GD1A. J Lipid Res 95. Korczak, B., P. Goss, B. Fernandez, M. Baker, and J.W. Dennis. 1994. Branching N-linked oligosaccharides in breast cancer. Adv Exp Med Biol 353:95-104. 96. Korczak, B., and J.W. Dennis. 1993. Inhibition of N-linked oligosaccharide processing in tumor cells is associated with enhanced tissue inhibitor of metalloproteinases (TIMP) gene expression. Int J Cancer 53:634-639. 97. Wang, R.J., C.H. Yang, and M.L. Hu. 1-Deoxynojirimycin inhibits metastasis of B16F10 melanoma cells by attenuating the activity and expression of matrix metalloproteinase-2/9 and altering cell surface glycosylation. J Agric Food Chem (In press). 98. Kosuge, T., T. Tamura, H. Nariuchi, and S. Toyoshima. 2000. Effect of inhibitors of glycoprotein processing on cytokine secretion and production in anti CD3-stimulated T cells. Biol Pharm Bull 23:1-5. 99. Dranoff, G. 2004. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 4:11-22. 100. Fisher, P.B., D. Sarkar, I.V. Lebedeva, L. Emdad, P. Gupta, M. Sauane, Z.Z. Su, S. Grant, P. Dent, D.T. Curiel, N. Senzer, and J. Nemunaitis. 2007. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24): novel gene therapeutic for metastatic melanoma. Toxicol Appl Pharmacol 224:300-307. 101. Morgan, R., G. Gao, J. Pawling, J.W. Dennis, M. Demetriou, and B. Li. 2004. N-acetylglucosaminyltransferase V (Mgat5)-mediated N-glycosylation negatively regulates Th1 cytokine production by T cells. J Immunol 173:7200-7208. 102. Ye, X.S., F. Sun, M. Liu, Q. Li, Y. Wang, G. Zhang, L.H. Zhang, and X.L. Zhang. 2005. Synthetic iminosugar derivatives as new potential immunosuppressive agents. J Med Chem 48:3688-3691. 103. Oka, H., Y. Shiraishi, H. Sasaki, K. Yoshinaga, Y. Emori, and M. Takei. 2003. Antimetastatic effect of an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis strain Aoyama B, Z-100, through the production of interleukin-12. Biol Pharm Bull 26:1336-1341.
本論文主要是探討桑之抗氧化能力及其活性成分 1-脫氧氮雜-D-葡萄糖 (1-Deoxynojirimycin, 1-DNJ) 之抗癌轉移能力。首先,利用不同抗氧化活性分析方法及主成份分析 5 個品系及 3 種成熟度之桑椹,此結果可提供基礎資訊作為選育高抗氧化活性之桑樹品系。其次,我們假設 1-DNJ 具有抗黑色素癌細胞轉移之能力,可能經由直接作用在癌細胞上及/或增強宿主的免疫反應上,為驗證上述假說,我們以具高轉移能力之小鼠黑色素癌細胞株 B16F10 細胞進行體外試驗,結果顯示 1-DNJ 可顯著抑制 B16F10 細胞之侵襲、移行及黏附,可能與抑制基質金屬蛋白酶 (matrix metalloproteinases, MMP) 2/9 活性及 mRNA 表現,與活化組織金屬蛋白酶抑制劑 (tissue inhibitors of metalloproteinase, TIMP) 2 mRNA 表現和改變細胞表面醣蛋白醣類殘基有關。此外,我們也發現 1-DNJ 與小鼠脾臟細胞共同培養後取得之條件培養液 (1-DNJ-CM) 亦可顯著抑制 B16F10 細胞之侵襲、移行及黏附,可能與同時增加脾臟細胞增生及細胞激素 (IL-2, 24, TNF-α, IL-8 and IL-10) mRNA 表現有關,基於上述結果,我們認為 1-DNJ 之抗轉移能力應與直接作用在癌細胞上及/或增強宿主的免疫反應均有關係。值得特別注意的是直接作用在癌細胞上所需之 1-DNJ 有效濃度遠高於增強宿主的免疫反應所需之濃度。綜合以上結果,本論文認為 1-DNJ 在抗 B16F10 細胞轉移上,免疫調節效果可能比直接抑制癌細胞的效果扮演更重要的角色。

This dissertation research concerns the antioxidant capacities of mulberry (Morus spp.) and the antimetastatic potentials of 1-deoxynojirimycin (1-DNJ), which is rich in mulberry. First, five genotypes (Miaoli No. 1, 73C020, 46C019, 74H3023, and 68H22024) and three maturity stages (unripe, medium ripe and fully ripe) of the mulberry (Morus sp.) fruit were analyzed by different antioxidant assay and principal component analysis. The results provided the basic data for choosing the genotype of mulberries with higher antioxidant activities. Second, we hypothesized that 1-DNJ could prevent metastasis of melanoma cells via the directory inhibitory effects and/or the immune-enhancing effects on cancer cells. To examine above hypothesis, we used a highly invasive melanoma cell line, B16F10 cells, and we found that 1-DNJ significantly inhibited the invasion, migration and adhesion, and that the effect was likely associated with attenuated activities and expression of matrix metalloproteinases (MMP)-2/9, enhancement of the tissue inhibitors of metalloproteinase (TIMP)-2 mRNA expression, and the alterations of the cell surface-binding motif. In addition, we further showed that 1-DNJ-conditioned media (1-DNJ-CM), which were obtained from the incubation of mouse splenocytes with 1-DNJ, significantly suppressed the invasion, migration and adhesion. The effect of 1-DNJ coincided with enhancement of splenocytes proliferation and the mRNA expression of cytokines (IL-2, 24, TNF-α, IL-8 and IL-10). The results stated above suggest that the antimetastatic potential of 1-DNJ may result from both the direct inhibitory and the immune-enhancing effects on cancer cells. It should be noted that the 1-DNJ concentrations required for the direct inhibition are much higher than those required for the immunomodulatory effect. Taken together, we conclude that immunomodulatory effect of 1-DNJ may play a more important role than the direct inhibitory effect on the antimetastatic activity against B16F10.
Appears in Collections:食品暨應用生物科技學系

Show full item record

Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.