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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
antioxidant capacity
principal component analysis
matrix metalloproteinases
tissue inhibitors of metalloproteinase
出版社: 食品暨應用生物科技學系所
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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.
摘要: 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.
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