熊果酸及齊墩果酸誘導人類肺癌細胞凋亡

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

黃雯雯(W. W. Huang) ； 楊家欣(J. S. Yang) ； 何偉真(W. J. Ho)

《通識教育學報》 9期 (2006/06) Pp. 245-256

https://doi.org/10.7107/JGED.200606.0245

摘要

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-H460)，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 300μg/ml；而oleanolic acid對上述細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細胞凋亡(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。

關鍵字

熊果酸 ； 齊墩果酸 ； 人類肺癌細胞株 ； 細胞凋亡

並列摘要

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 300μg/ml, respectively.
But OA seemed to have no cytotoxic effect on CH27, NCI-H460 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.

並列關鍵字

ursolic acid ； oleanolic acid ； human lung cancer cell lines ； apoptosis

參考文獻

Kuo, Kou-Wha,Shu-Hui Hsu,Yun-Ping Li,Wei-Ling Lin,Li-Feng Liu,Li-Ching Chang,Chih-Chao Lin,Chun-Nan Lin,Hamm-Ming Sheu(2000).Anticancer activity evaluation of the Solanum glycoalkaloid solamargine: Triggering apoptosis in human hepatoma cells.Biochemical Pharmacology.60(12),1865-1873.

Hsu SH. TR. Tsai,CN. Lin,MH. Yen,KW. Kuo(1996).Solamargine purified from Solanum incanum Chinese herb triggers gene expression of human TNFR I which may lead to cell apoptosis.Biochemical & Biophysical Research Communications.229(1),1-5.

Lin CN.,CM. Lu,MK. Cheng,KH. Gas,SJ. Won(1990).The cytotoxic principles of Solanum incanum.Journal of Natural Products.53(2),513-516.

Chang, CI.,CC. Kuo,JY. Chang,YH. Kuo(2004).Three new oleanane-type triterpenes from Ludwigia octoralvis with cytotoxic activity against two human cancer cell lines.Journal of Natural Products.67(1),91-93.

Harmand PO.,R. Duval,B. Liagre,C. Jayat-Vignoles,JL. Beneytout,C. Delage,A. Simon(2003).Ursolic acid induces apoptosis through caspase-3 activation and cell cycle arrest in HaCat cells.International Journal of Oncology.23(1),105-112.