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  • 學位論文

山葵萃取物對於肝癌治療性之探討

The therapeutic study of Wasabia japonica extract in liver cancer

指導教授 : 周芬碧

摘要


在日本及台灣,山葵是一種被廣泛使用的食材香料,山葵中的異硫氰酸鹽具有排毒、抗發炎和誘發癌細胞的細胞凋亡。從HPLC和LC-MC/MC的檢測中發現我們的山葵水萃物含有5-(Methylsulfinyl) pentyl ITC、6-(Methylsulfinyl) hexyl ITC和7-(Methylsulfinyl) heptyl ITC這三種成份。在Hep3B 和HepG2 人類肝癌細胞加入山葵萃取物(0.25至1 mg/ml) 會引起強烈的毒殺效果。進一步利用DNA condesation、流式細胞儀及西方點墨法也證實了山葵萃取物擁有毒殺肝癌細胞的效果是透過誘發ROS的累積,並且是透過DNA傷害及經由p73 及p53 調節的內源性和外源性的細胞凋亡路徑。在HepG2 細胞中發現處理WJE 48 小時後AVOs 的表現量隨著濃度增加而增加,LC3 II的蛋白表現量也明顯的增加。動物實驗部份,我們利用異種移植的模式,也確定了山葵萃取物能透過細胞實驗結果的類似路徑抑制腫瘤的生長。我們的實驗結果也是首次證實從新鮮山葵中萃取出的物質能有抗肝癌的效果及誘發細胞產生autophgay,期望本研究的發現,使山葵能在未來肝癌治療的應用上提供一個新的方式。

關鍵字

山葵 肝癌

並列摘要


Wasabia japonica (WJ) is widely used as a food spice in Japan and Taiwan. Wasabia isothiocyanates have effects of detoxification, anti-inflammation, and inducing cancer cell apoptosis. HPLC and LC-MC/MC analysis of the water extract of WJ (WJE) prepared in this study contained 5-(Methylsulfinyl) pentyl ITC, 6-(Methylsulfinyl) hexyl ITC and 7-(Methylsulfinyl) heptyl ITC. WJE (0.25 to 1 mg/ml) induced a strong cytotoxic effect toward Hep3B and HepG2 cells. As evidenced by DNA condensation, flow cytometry and Western blotting, the cytotoxicity of WJE was exerted by inducing ROS accumulation, DNA damage and the p73 and p53-mediated apoptotic death through both intrinsic and extrinsic pathways. The results showed a dose-dependent formation of acidic vascular organelles when HepG2 cells were treated with WJE for 48 h. An increase in the protein level of LC3 II was confirmed. The xenograft model demonstrated that WJE was able to suppress tumor growth via a mechanism similar to the cellular studies. The results are the first to demonstrate the anti-cancerous activities of WJ extract prepared from fresh wasabi rhizomes and autophagy induced by WJ extract in liver cancer cells, and this investigation supports the future application of WJ in liver cancer therapy.

並列關鍵字

Wasabia japonica liver cancer

參考文獻


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