葛根含藥血清及相關黃酮誘導人類乳癌細胞的細胞凋亡

Serum metabolite of Puerariae Radix and related flavonoids induce apoptosis in human breast cancer cells

林佳宏(Chia-Hung Lin)

指導教授 ： 蔡輔仁 ； 萬 磊

亞洲大學/健康學院/生物科技學系碩士班/碩士(2008年)

摘要

黃酮類物質（Flavonoid）是構成植物中多酚類的主要成分，它是一群來自於水果、蔬菜、葡萄酒、茶的化合物。黃酮類物質可以被分為六個亞綱，分別為flavones, flavanones, flavanols, flavonols, isoflavones, 和anthocyanidins.葛根是一種普遍的中藥和食物，而 puerarin, daidzein,and genistein為異黃酮的一種，是葛根內的主要成分，它們具有抗血栓，抗過敏及活化雌激素的功能。另外異黃酮具有降血脂保護血管，降低氧化壓力，降低癌症發生和調整免疫反應。最近的研究證實異黃酮具有對抗癌症的能力，因此我將研究葛根含藥血清及相關的異黃酮是否可以誘導人類乳癌細胞的細胞凋亡。在研究結果發現，葛根含藥血清造成凋亡細胞相關蛋白caspase-3的活性增加，caspase-9, p53, p21,和Bax蛋白質的改變。而葛根主要成分異黃酮，也造成caspase-3的活性增加，細胞週期的改變。我的研究結果證實葛根含藥血清及相關異黃酮的確可以降低人類乳癌細胞的增生，並且誘導細胞凋亡的發生。在另一個方面，我們研究了黃酮類對於乳癌細胞生長的影響。我們發現7.8-dihydroxyflavone, flavones, apigenin和luteolin會誘導乳癌細胞的凋亡並且是透過活化Foxo3a這個基因的表現來促進乳癌細胞凋亡。

關鍵字

乳癌 ； 細胞凋亡

並列摘要

Flavonoids constitute the largest and most important group of polyphenolic compounds in plants. They are widely distributed in many frequently consumed beverages and food products of plant origin such as fruit, vegetables, wine and tea.
Depending on their oxidation state and functional groups, flavonoids are further divided in six subclasses: flavones, flavanones, flavanols, flavonols, isoflavones, and anthocyanidins .Puerarin, daidzein, and genistein isolated from Puerariae Radix (PR), a popular Chinese herb and a food, have antithrombotic, anti-allergic and estrogenic activities. In addition, they decrease blood lipid levels, reduce oxidative stress, lower cancer risk, cardio-protective, and modulate immune responses. Recent studies demonstrated that isoflavones also possessed anti-cancer properties. Therefore, we investigated the effects of serum metabolite of PR and related isoflavones on inducing apoptosis of breast cancer cell lines. We investigated the effect of serum metabolite of PR on the protein expression of apoptosis-associated genes. The results revealed increased activities of Caspase-3, caspase-9, p53, p21, and Bax. The results revealed that increased caspase-3 activities and modification of the cell cycle caused by the Serum metabolite of Puerariae Radix and related isoflavones. In this report, we investigated the effect of flavonoids on the breast cancer cell of growth. In addition, We also evaluated other flavonoids such as on the growth of breast cancer cell. It result that this flavonids can inhibit the growth of breast cancer cell through inducing apoptosis by activation the Foxo3a.

參考文獻

1. MacGregor, J.I. and V.C. Jordan, Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev, 1998. 50(2): p. 151‐96.

2. Sommer, S. and S.A. Fuqua, Estrogen receptor and breast cancer. Semin Cancer Biol, 2001. 11(5): p. 339‐52.

3. Cummings, S.R., et al., Serum estradiol level and risk of breast cancer during treatment with raloxifene. Jama, 2002. 287(2): p. 216‐20.

4. Hanahan, D. and R.A. Weinberg, The hallmarks of cancer. Cell, 2000. 100(1): p. 57‐70.

5. Kelsey, J.L. and L. Bernstein, Epidemiology and prevention of breast cancer. Annu Rev Public Health, 1996. 17: p. 47‐67.