臺灣博碩士論文加值系統

没食子酸丙酯(propyl gallate, PG)具有三個OH基的人工合成酯類，因其結構的關係具有抗氧化的特性，另外PG也具有清除自由基、抗細菌、抗真菌、抗齬齒及抗發炎等生理活性，但是對於細胞內抗發炎機制以及抗腫瘤的影響卻尚未明瞭。
在本篇論文中證實PG抑制12-O-tetradecanoyl-phorbol-13-acetate (TPA)誘導THP-1細胞發炎反應，是藉由抑制第二型環氧酵素(COX-2)、前列腺素E2 (PGE2)合成釋放，propyl gallate也會降低核內NF-B的p65、細胞質內磷酸化IB、p65-(Ser-536)及IKK表現量。在抗癌方面指出較高濃度的propyl gallate 會降低血癌細胞(THP-1、Jurkat和HL-60)存活率，並且會明顯地造成THP-1細胞型態的改變、DNA濃縮斷裂、等現象進而誘導THP-1細胞凋亡。
綜合上述研究結果推測PG成為抗發炎劑且有潛力發展成化學癌症預防的藥物，特別針對在血癌病患的治療上。

Propyl gallate (PG), an ester also known as propyl 3,4,5-trihydroxybenzoate that belongs to the polyphenolic compound family is synthesized by the condensation of propanol and gallic acid. As synthetic antioxidant, PG has been used in processed food and medicinal preparations. The biological activity of propyl gallate is consistent with its free-radical ability, antimicrobial activity, antifungal activity, antibacterial activity, anticariogenesis and anti-inflammatory. Up to now, the anti-cancer effect and anti-inflammatory mechanism of PG are unclear.
In the present study, we investigated the effects of PG on the expression of COX-2 and prostgrandin E2 production in 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced THP-1 cells. Moreover, PG reduced the levels of p65, a functionally active subunit of NF-B in nuclear fractions prepared from TPA-induced THP-1 cells. PG also inhibited phosphorylation of p65-(Ser-536) and IKK induced by TPA. On the other hand, PG reduced the viability of THP-1, Jurkat, and HL-60 leukemia cells. In addition, we observed DNA condensation, morphology changed and induced apoptosis in THP-1 cells.
As a potential chemopreventative agent and anti-inflammatory agent, PG might serve as a food supplement for human leukemia patients.

目錄 I
縮寫表 III
中文摘要 V
英文摘要 VI
第一章緒論 1
第一節炎症與癌症………………………………………………………………1
第二節没食子酸丙脂(Propyl gallate) 2
第三節NF-kB與環氧酵素 4
第四節細胞凋亡 9
第五節血癌 11
第二章 研究目的及動機 14
第三章 材料與方法 15
第一節材料 15
一、細胞株 15
二、細胞培養 15
三、細胞凋亡 16
四、抗體 16
五、其他藥品 17
六、實驗儀器 18
第二節方法 19
一、懸浮細胞培養 19
二、利用Flow cytometry分析細胞週期 19
三、利用Hoechest33258染色法觀察細胞內DNA聚集現象 20
四、利用四氮唑藍比色法( MTT assay )測定細胞存活率與細胞毒性 20
五、利用西方墨點法分析細胞內蛋白表現 21
六、偵測Prostaglandin E2 (PGE2) 含量 24
七、利用Annexin V-FITC與PI雙染觀察細胞apoptosis情形 25
八、統計方法 26
第四章 結果 27
第一節、Propyl gallate誘導血癌細胞凋亡之影響 27
一、Propyl gallate對血癌細胞毒殺性(存活率)試驗的評估 27
二、Propyl gallate造成血癌細胞型態改變 27
三、Propyl gallate造成血癌細胞DNA濃縮情形 28
四、Propyl gallate對血癌細胞週期之影響 28
五、Propyl gallate誘導血癌細胞凋亡之影響 29
六、Propyl gallate誘導THP-1細胞凋亡主要路徑之探討 30
第二節Propyl gallate預防細胞發炎反應之結果探討 32
一、Propyl gallate抑制TPA誘導THP-1產生COX-2表現量之影響 32
二、Propyl gallate抑制TPA誘導THP-1釋放PGE2 32
三、Propyl gallate抑制TPA誘導THP-1活化NF-kB路徑之影響 33
第五章 討論 34
第六章 結論 39
第七章 參考文獻 40
第八章 圖……………………………………………………………….48
第九章 附錄…………………………………………………………….63

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