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標題: | 落花生二苯乙烯類對HL-60細胞株的影響 The effects of peanut stilbenoids on HL-60 cell line |
作者: | Ping-Chen Chung 鍾秉真 |
指導教授: | 林淑萍(Shwu-Bin Lin) |
關鍵字: | 二苯乙烯類,細胞凋亡,拓樸異構酶,II, stilbenoids,Apoptosis,Topoisomerase II, |
出版年 : | 2008 |
學位: | 碩士 |
摘要: | 二苯乙烯類 (stilbenoids)為植物抵抗黴菌或病蟲害的天然抗生素,許多研究報告指出,二苯乙烯類具有抗氧化、抗發炎、防癌及抗癌等生理活性。本論文研究純化自花生仁的二苯乙烯類,包括resveratrol (RSV)、arachindin-1 (Ara-1)、arachindin-3 (Ara-3)及isopentadienylresveratrol (IPD)的抗癌活性,以HL-60血癌細胞株當作實驗模型,研究中發現,RSV、Ara-1及Ara-3可抑制HL-60細胞株的生長,其中,Ara-1在較低的濃度就可以抑制細胞生長 (EC50為4.2 μM)。以Ara-1處理HL-60細胞,在短時間內可造成細胞粒線體膜電位的下降、caspases的活化、DNA斷裂以及細胞週期改變。Ara-3處理HL-60細胞則是觀察到其細胞膜完整性的改變、細胞粒線體膜電位的下降,以及caspases的活化。綜合以上結果,Ara-1及Ara-3處理HL-60細胞皆可以引發細胞走向凋亡,而對正常不增生的周邊血單核球細胞則無影響,因此具有成為抗癌藥物的潛力。由於體外試驗Ara-1可抑制Topoisomerase II的活性,但對HL-60與HL-60/MX2 (Topoisomerase II缺乏的HL-60突變株)的毒性沒有差異,推測Ara-1造成細胞走向凋亡並非透過抑制Topoisomerase II。但仍可由以上結果顯示,Ara-1及Ara-3可能具有抗癌的潛力。 Stilbenoids are phytoalexins produced by plants under attack by pathogens such as fungi. Previous sutdies have demonstrated that stilbenoids have bioactivities such as anti-oxidation, anti-inflammation, cancer chemoprevention and anti-carcinogenic effect. In this study, resveratrol (RSV), arachidin-1 (Ara-1), arachidin-3 (Ara-3), and isopentadienylresveratrol (IPD) were isolated from peanuts. RSV, Ara-1 and Ara-3 display cytotoxic effect on HL-60, and Ara-1 is the most toxic. Further study showed that Ara-1 treatment on HL-60 cells caused loss of mitochondrial membrane potential (MMP), caspases activation, and changes in cell cycle distribution. Ara-3 treatment on HL-60 cells caused loss of MMP and cell membrane integrity as well as caspases activation. These results suggested that Ara-1 and Ara-3 are potential anticancer agents that induced cancer cell apoptosis. Ara-1 and RSV are cytotoxic to proliferating cells, HL-60, but did not affect on nonproliferating human peripheral blood mononuclear cells. Furthermore, Ara-1 was found to inhibit the activity of topoisomerase II in vitro, but showed no significant difference in cytotoxicity between HL-60 and Topo II defective HL-60/MX2 cells. Topoisomerase II inhibition may not be involved in the mechanisms of apoptosis induction by Ara-1 in HL-60 cells. These results indicate that Ara-1 and Ara-3 are potential anti-cancer agents. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37354 |
全文授權: | 有償授權 |
顯示於系所單位: | 醫學檢驗暨生物技術學系 |
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