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Title: 新穎組蛋白去乙瞳醇抑制劑的抑癌能力探討
Other Titles: Anticancer Effect of a Novel Histone Deacetylase Inhibitor in Cell Model
Authors: 賀信銘
Issue Date: Dec-2010
Publisher: 國立臺灣師範大學生命科學學系
Department of Life Science, NTNU
Abstract: 前人研究發現,但蛋白去乙越筒,(Histone deacetylas間. HDACs) 在許多遍症腫續中有過量表現成過度活化的現車,因此HDACs 1l,具有潛力的措症治療橡靶﹒在現行的血滾越續臨床治療上,但蛋白去乙鐘前抑制劑。王DACi) 已橙實具有多重抑瘤能力;然而. HDACi 對於團體腫瘤的療致仍符進-步研究﹒本篇研究提出一個新穎的HDACi - N-hydroxy-4-((IR, 2R)-2-phenylcycloproppanecarboxamido)benzamide(HP CPCB) 以探討其作為治療固體腫瘤的可行性﹒我們首先利用多種肺瘖、乳瘖細胞株和正常肺細胞、軍L屠細胞測試t佇CPCB 的細胞4年怯和專一性,接著利用流式細胞儀(F low cytometry) 觀測到HPCPCB 處理過的個胞,會有細胞過期GI 期停滯的現象﹒從西方點墨法(Western blot) 發現HPCPCB 會抑制或延邊GI 細胞過期調控蛋白CDC25A 、CDK4 及cyclin E 的表現壘,並且提高細胞迪斯抑制蛋白p21 的表現量﹒此外,看娃們旦進-步控明. HPCPCB 會抑制HDAC 的活性,並會引起組蛋白H3 及H4· 和非但蛋白p53 及tubulin 的乙越化程度增加﹒我們的實驗結果顯示,HPCPCB 是一有欽的HDAC 抑制劑,益有進一步作為通症治療用黨的研究可行性﹒
Histone deacetylases (HDACs) are potential therapeutic targets for the treatment of hematologic and solid tumor malignancies due to their Qverexpression and/or increased activity in various cancers Although HDAC inhibitors exhibit significant inhibition ability in hematological cancers,their effect in solid tumors has not been satisfactory. Here, we propose a novel HDAC inhibitor, N-hydroxy-4-«(l R,2R)2- phenylcyclopropanecarboxamido)benzamide (HPCPC8), as a chemotherapeutic drug for solid tumors First, we examined the cytotoxicity of HPCPC8 in various lung and breast cancer cells and their corresponding nonnal cells using MIT assay. HPCPCB showed significant growth inhibition on various cancer cells, while there was no serious cytotoxicity against normal cells. Results of flow cytometry showed that HPCPC8 caused cell cycle arrest at GI phase. Western blotting indicated that proteins required for cell cycle progression such as COC25A, COK4 and cyclin E were reduced and the cell cycle inhibitor p21 was up-regulated by HPCPC8 treatment. Furthennore, HPCPCB inhibited HDAC activity and induced an increase in acetylated histone proteins H3 and H4 and non-histone proteins p53 andd tubulin. Our findings suggest that HPCPC8 is a potent HDAC inhibitor and has potential in cancer treatment.
Other Identifiers: C56841C2-63B2-DC3D-133F-D8FB08F0FF2D
Appears in Collections:生物學報

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