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題 名 | 天然產物抗人類肝細胞癌活性之研究:芸香科生物鹼之篩選=Screening of Natural Products with Antitumor Activity on Human Hepatocellular Carcinoma: Rutaceous Alkaloids |
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作 者 | 蔡榮發; | 書刊名 | 中醫藥年報 |
卷 期 | 17:3 1999.05[民88.05] |
頁 次 | 頁75-195 |
分類號 | 414.32 |
關鍵詞 | 芸香科生物鹼; 肝細胞癌; 預設性細胞死亡; Hepatocellular carcinoma; Rutaceous alkaloid; Apoptosis; |
語 文 | 中文(Chinese) |
中文摘要 | 肝細胞癌(以下簡稱肝癌)是國人最常見癌症死因之一。肝癌的治療效果仍然不盡理想,缺少有效抗癌藥物是一大主因。因此,抗癌藥物的研發,重要性不言可喻。運用現代進步的基礎與臨床醫學資訊,與生物科技以從事天然植物抗癌或防癌成分之研究,終將為癌症的治療帶來新希望。本研究的目的,就是要篩選出具治療肝癌潛力的芸香科生物鹼。 本研究利用肝癌細胞株做為研究對象,加入不同濃度(0,0.05, 0.5,5,50,及500nmole)之純化芸香科生物鹼(共60種),研究下列數種抗肝癌活性:1)抑制肝癌細胞增生;2)抑制肝癌細胞去氧核醣核酸合成;3)促進肝癌細胞apoptosis(並進行細胞週期分析);4)促進肝癌細胞壞死(測定lactate dehydrogenase);5)抑制肝癌細胞topoisomerase Ⅰ活性;6)對肝癌細胞甲型胎兒蛋白的濃渡的影響。結果發現13.3%純化之芸香科性物鹼(包括Dictamine、γ-fagarine、robustine、zanthosimuline、toddaquinoline、2H-isoterihanine、toddaliamide、及canthin-6-one)對肝癌細胞增生及肝癌細胞去氧核醣核酸合成有抑制作用,這些抑制作用與生物鹼濃度成正比。且能使肝癌細胞去氧核醣核酸產生裂解現象。肝癌細胞加入生物鹼前後LDH濃度無差異,表示這8種生物鹼只會讓肝癌細胞發生apoptosis(預設性細胞死亡),而不會讓肝癌細胞發生急性細胞毒性(cytopathy),產生壞死( necrosis)。但因所有芸香科生物鹼均無抑制第一型拓樸脢活性能力,表示apoptosis基轉與第一型拓樸脢無關,確實基轉有待進一步探討。建議:對於能造成apoptosis的芸香科生物鹼,值得進一步作其毒理研究與臨床試驗,以決定其成為抗癌新藥之可能性。 |
英文摘要 | Hepatocellular carcinoma (HCC) is one of the most frequent cancers in Taiwan. The poor survival was due to lack of specific anti-cancer drugs. It is imperative to develop new drugs for efficient therapy. This study aims to screen retaceous alkaloids with anti-tumor activity for HCC. Different concentations of purified rutaceous alkaloid were added to hepatoma cells in culture to evaluate the anti-tumor activiity. The following anti-cancer activities will be assessed in 61 kinds of purified rutaceous alkaloids: inhibition of hepatoma cell proliferation, inhibition of DNA synthesis, induction of apoptosis, inhibition of topoisomerase I activity, evaluation of necrosis by determining the level of lactate dehydrogenase in the culture medium, and determination of alphafetoprotein in the cultured medium. The results are as follows: Eight (13.3%) of 60 kinds of rutaceous alkaloid had inhibition on cell proliferation and DNA synthesis of hepatoma cells. The activity of inhibition correlates with alkaloid concentration. These alkaloids included Dictamine, g-fagarine, robustine, zanthosimuline, toddaquinoline, 2H-isoterihanine, toddaliamide and canthin-6-one. DNA fragmentation assay indicated that these alkaloids had apopotosis phenomenon, but without causing immediated cell necrosis (as evidenced by normal LDH activity). There is no inhibitory activity on topoisomerase I, suggesting that apoptosis derived from mechanisms other than topoisomerase inhibition. In vonclusion, this study indicated that some urtaneous alkaloids can cause apoptosis of hepatoma cells and wothout cytopathy. We suggest to screen other rutaceous alkaloids for anto-cancer activity of HCC Moreover, toxicological study and clinical research about rutaceous alkaloids with apoptosis is necessary. |
本系統中英文摘要資訊取自各篇刊載內容。