Pentacyclic triterpene類化合物——熊果酸及齊敦果酸誘導人類肺癌細胞凋亡

Ursolic Acid and Oleanolic Acid Induced Apoptosis in Human Lung Cancer Cells

熊果酸（ursolic acid）及齊墩果酸（oleanolic acid）皆屬pentacyclic triterpene化合物，有研究顯示此類化合物具細胞毒殺作用（cytotoxicity），可誘導細胞分化（differentiation），並有抗突變（antimutagenic）作用及抗病毒（antiviral）等活性。我們研究發現ursolic acid對人類血癌細胞株（K562，U937），人類大細胞肺癌株（NCI-460），人類肺癌鱗狀上皮細胞株（CH-27），人類肺癌細胞株（H1355）皆具抑制效果，其中對CH-27細胞株，NCI-H460細胞株，H1355細胞株，抑制效果更為顯著，IC50分別為50、100 and 300 µg／ml；而oleanolic acid對上述胞株的毒殺作用似乎並不明顯。為更進一步探討熊果酸（ursolic acid）之抗癌機制，因此我們以熊果酸處理CH27細胞，進行DNA電泳分析，發現有DNA裂解現象，至於細胞周期試驗顯示無論是熊果酸還是齊墩果酸對CH27細胞株的細胞周期無明顯滯留現象，顯示二者沒有抑制細胞周期的作用。經西方墨點法測試蛋白質，結果顯示Bcl-2蛋白質的量隨處理時間增長而增加，而Bax蛋白質量則有下降的趨勢，顯示其抑制癌細胞生長的作用可能是藉由紬胞凋亡（apoptosis）的途徑產生，造成凋亡的原因可能是透過與Bcl-Xs蛋白質相關機制，同時Bax蛋白質量降低亦是熊果酸導致細胞凋亡的機轉之一，值得作更深入之探討。

The compounds of pentacyclic triterpene (include ursolic acid and oleanolic acid) have been reported to raise anti-tumor activities. In this study, we investigated the anti-tumor effects of ursolic acid (UA) and oleanolic acid (OA) on human lung squamous cancer CH-27 cells, human lung large cell carcinoma NCI-H460 cells and human lung cancer H1355 cells lines. UA inhibited the cell proliferation with dose- and time- dependence, and the IC50 of UA on CH27, NCI-H460 and H1355 cells were 50, 100 and 300 µg/ml, respectively. But OA seemed to have no cytotoxic effect on CH27, NCLH460 and H1355 cells. UA showed to have better inhibitory effect on CH-27 than the other two (NCI-H460, H1355). We focused on the apoptosis experiment of CH-27 cells and found a phenomenon of DNA fragmentation. Our results were consistent with the published research data as evidenced by the up-regulation of pro-apoptotic Bax protein and the down-regulation of anti-apoptotic Bcl-2 protein during UA induced apoptosis. The precise mechanism of the induction of apoptosis by UA in CH27 cells will be the subject for further investigation in our research.