- 學位論文
香葉木素(Diosmetin)誘發人類血癌細胞HL-60凋亡之機制探討
The Mechanism of Diosmetin Induced Apoptosis in Human Leukemia Cancer Cell Lines HL-60
摘要
本研究之目的為探討香葉木素（Diosmetin）是否會引起癌細胞凋亡以及誘發凋亡之機制的探討。 實驗結果發現血癌細胞HL-60在以Diosmetin 100μM之濃度處理後，其誘導細胞凋亡百分比達49.34%，且在加藥處理6小時即可見DNA片段化產生，6到16小時之間呈現漸增之趨勢。另外Diosmetin會減低粒腺體膜電位，進而導致cytochrome c釋出至細胞質內，誘導原型caspase-9與caspase-3活化，進而引起PARP去活化及DFF45裂解。另一方面，Diosmetin促使caspase-8之活化，並進而使Bid水解形成t-Bid，其也可能誘使cytochrome c釋出。Diosmetin所引起hydrogen peroxide和superoxide增加也可能造成氧化壓力增加，進而引起細胞凋亡。在Bcl-2家族蛋白中，經由Diosmetin處理後可降低抑制細胞凋亡之Bcl-2及Bcl-xL的表現，以及促進細胞凋亡的Bad和Bax之裂解活化，進而促使血癌細胞HL-60凋亡。 綜合以上實驗結果，可以證實Diosmetin具有誘發血癌細胞HL-60凋亡，且在促進細胞凋亡的機轉中，經由粒腺體釋出cytochrome c之途徑扮演了重要的角色；因此Diosmetin誘發癌細胞凋亡在癌症治療及預防上，可能提供重要的機制。 關鍵字：香葉木素（Diosmetin）、cytochrome c、caspase-9、caspase-3、 caspase-8、t-Bid、Bcl-2家族蛋白
並列摘要
The purpose of this research is to study the Diosmetin if will cause the apoptosis of cancer cell and the mechanism of the induction of apoptosis by Diosmetin. In our study, Diosmetin has shown its apoptosis-inducing potency in HL-60 with its 49.34% apoptotic ratio of 100μM treatment. When HL-60 were treated with 100μΜ of Diosmetin, DNA ladder were visible at 6 hours and increased from 6-16 hours after treatment. Diosmetin could decrease the mitochondrial membrane potential （ΔΨm）, trigger cytochrome c released to cytosol, and subsequently induced the process of procaspase-9 and procaspase-3, which were followed by the cleavage of PARP and DFF-45. On the other hand, the caspase-8 could be induced and cause the development of truncated Bid and induced cytochrome c released. The hydrogen peroxide and superoxide increase might result oxidative stress increased and induced apoptosis. The cleavage of the proapoptotic Bcl-2 proteins, such as Bad and Bax to produce their truncated forms, and the down-regulation of Bcl-2 were detected in our study. From these results, we suggest that mitochondria might play an important role in the Diosmetin-induced apoptosis. The induction of apoptosis by Diosmetin may offer a pivotal mechanism for its cancer-therapeutic and cancer-preventive effects. Key word：Diosmetin、cytochrome c、caspase-9、caspase-3、 caspase-8、t-Bid、Bcl-2 family protein
參考文獻
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