Ellagic acid (EA)是存在莓類、水果和堅果中的一種多酚類化合物。在過去的研究中顯示可以抑制癌症的生長與促使癌症細胞的凋亡。雖然EA已經被研究指出具有抗癌的活性，卻沒有明確的證據指出可以誘發人類膀胱癌細胞TSHG-8301的細胞凋亡。因此在本論文中探討EA是否可以誘發膀胱癌細胞TSHG-8301的細胞凋亡。首先我們利用MTT assay測試處理完不同濃度的EA並培養不同時間後的細胞存活率。我們也利用的流式細胞儀去偵測細胞中的細胞週期、粒線體膜電位變化、活性氧基群的表現、以及細胞質中鈣離子濃度的變化，最後再利用流式細胞儀去偵測caspase-3的活性與Annexin V親和力分析，藉此進一步的確認細胞凋亡的現象。實驗結果顯示EA可以抑制細胞的生長。EA也會使細胞中的粒腺體膜電位下降，並且造成DNA的與染色體凝集。由西方墨點法分析發現Bid與Bax表現明顯的增加，同時也發現 cytochrome c、AIF 與Endo G 由粒線體中釋放出來並造成下游路徑的活化並造成細胞凋亡。總觀以上結果我們認為EA可以引起粒線體功能的缺失並導致細胞毒性，且使粒線體膜電位下降與引起DNA的損傷最後導致細胞死亡。
Ellagic acid (EA), a polyphenolic compound which was found in berries, fruits and nuts, has been shown to possess growth inhibition and apoptosis promoting activities in cancer cell lines. Although EA has been reported with anticancer activity, there are no direct evidences for EA induces apoptosis in human bladder carcinoma TSGH-8301 cells. In this study, we investigated EA whether or not can induce apoptosis in TSGH-8301 cells. We use MTT assay to determine cell viability from TSGH-8301 cells after treated with different doses of EA and for various time periods. We also used the flow cytometry to examine the levels of mitochondrial membrane potential, the production of reactive oxygen species and the levels of calcium ion after TSGH-8301 cells treated with various doses of EA. Finally, we used the flow cytometry to examine caspase-3 activity and Annexin V affinity assay for apoptosis. Our results indicated that the proliferation of TSGH-8301 cells was inhibited after treated with EA (50?嵱) for 48 hours. EA also caused decreased the levels of MMP in TSGH-8301 cells. In nuclear, we seen the chromatins began to condense in TSGH-8301 cells after EA (50?嵱) treated for 24 hours. Then, DNA was damaged after EA treated for 48 hours. In Western blotting assay, we found Bid and Bax were expressed and cytochrome c, AIF and Endo G were released from mitochondria and activated downstream pathway to cause cell apoptosis. In conclusion, we suggest that EA caused the dysfunction of mitochondria followed by causing cytotoxicity, DNA damaged and MMP decreased, then led to cell death.
