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題 名 | 抗癌中藥單離成分對實驗腫瘤細胞生長抑制之分析 |
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作 者 | 林榮耀; | 書刊名 | 中醫藥年報 |
卷 期 | 15:2 1997.05[民86.05] |
頁 次 | 頁1-47 |
分類號 | 414.5 |
關鍵詞 | 拓蹼脢; 計畫性死亡; 抗腫瘤; Topoisomerase; Apoptosis; Cancer chemotherapy; |
語 文 | 中文(Chinese) |
中文摘要 | 細胞內DNA的拓樸狀態 ( topology ) 受拓樸脢 ( topoisomerase ) 所主宰 。 拓樸脢參與複製 (replication ) 轉譯 (transcription )、 重組 (recombination ) 及修 復 (repair ) 等 DNA 代謝中重要反應。 喜樹精 (camptothecin) 因為它能穩定拓樸脢與 DNA 所形成的共價化合物,使 DNA 的缺口無法連接回來,而造成細胞毒性 (cytotoxicity) , 所以被拿來作為因能有效抑制第一型拓樸脢的抗癌藥物。 本計畫利用 Topoisomerase I relaxation assay 証實了兩大類有效第一型拓樸活性的抑制物, 分別來自中藥波羅蜜的單 離成分及 Quinolone 類的化學合成藥物。由於藥物作用到 DNA 與拓樸脢共價化合物上,使 細胞內堆積許多有缺口的 DNA 與蛋白的化合物, 這時候拓樸脢的存在反而成為細胞的毒性 物。因 DNA 的斷裂,接著許多重要的代謝也被迫停止,最後造成細胞死亡 (apoptosis )。 已有報告指出 camptothecin 會造成人類血癌細胞株 HL-60 進行計畫性死亡 (apoptosis) ,本計畫篩選出的兩類藥物,也藉由一些細胞進行有計畫性死亡的特徵,來觀察這些藥物對 HL-60 細胞株的毒性; 這些特徵在本論文主要分成兩大類, 分別是: (1) 當細胞進行 apoptosis 由於活化了細胞內核酸分解脢 (endonuclease ),而造成 DNA,小片段的斷裂, 藥處理過後的細胞株,可將萃取出來 DNA 交由凝膠電泳 (agarose gel electrophoresis ) 分析出小片段的 DNA。(2 ) 在細胞型態 (cell morphology ) 方面,進行 apoptosis 的細 胞也可以觀察出特殊的型態, 如細胞質內有泡狀物 (vacuolated cytoplasma) 形成及染色 質被染色後有較深 (chromatin condensation ) 的特徵出現。 經由本計畫研究的結果,我 們希望能進一步藉由研究造成細胞進行有計畫性死亡的基因產物,而能深入瞭解細胞對藥物 的敏感性 (sensitivity) 或抗藥性 (resistance),以期將來發展新一代的抗腫瘤藥物。 |
英文摘要 | In the cells, the topology of DNA is orchestrated by enzymes known as topoisomerases. Topoisomerases are involved in many aspects of DNA metabolism such as replication, transcription, recombination, and repair reactions. Camptothecin, which stabolizes the covalent intermediate of topoisomerase I and DNA is an effective drug for cancer chemotherapy. In this study, two new kinds of topoisomerase I inhibitor purified from the Chinese herb (Artocarpus heterophyllus) and synthetic quinolone derivative have been demonstrated to be strong topoisomerase inhibitors by using 'topoisomerase I relaxation assay'. The topoisomerase I inhibitor camptothecin, was shown to induce apoptosis (programmed cell death) of human prom elogenous leukemia HL-60 cells. The two new kinds of topoisomerase I inhibitors which we have identified in this study, also can induce apoptosis of HL-60 cells through the following mechanisms: <<a>> activation of an endonuclease in apoptotic cells resulted in the formation of low molecular weight DNA fragments which were confirmed by agarose gel electrophoresis. <<b>> Changes in cellular morphology of apoptotic cells resulted in the early appearance of shrunken cells with vacuolated cytoplasma and regions of intense chromatin staining around the nuclear periphery. By this study, we hope to identify the compounds which induce the programmed cancer cell death, which will be important sources for new types of antitumor drugs. |
本系統中英文摘要資訊取自各篇刊載內容。