前人研究發現，組蛋白去乙醯酶 (Histone deacetylases, HDACs) 在許多癌症腫瘤中有過量表現或過度活化的現象，因此HDACs 為具有潛力的癌症治療標靶。在現行的血液腫瘤臨床治療上，組蛋白去乙醯酶抑制劑 (HDACi) 已證實具有多重抑癌能力；然而，HDACi 對於固體腫瘤的療效仍待進一步研究。本篇研究提出一個新穎的HDACi－N-hydroxy-4-((1R,2R)-2-phenylcyclopropanecarboxamido) benzamide(HPCPCB) 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癌、乳癌細胞株和正常肺細胞、乳房細胞測試HPCPCB 的細胞毒性和專一性；接著利用流式細胞儀 (Flow cytometry) 觀測到HPCPCB 處理過的細胞，會有細胞週期G1 期停滯的現象。從西方點墨法 (Western blot) 發現HPCPCB 會抑制或延遲G1 細胞週期調控蛋白CDC25A、CDK4 及 cyclin E 的表現量，並且提高細胞週期抑制蛋白p21 的表現量。此外，我們更進一步證明，HPCPCB 會抑制HDAC 的活性，並會引起組蛋白H3 及H4，和非組蛋白p53 及tubulin 的乙醯化程度增加。我們的實驗結果顯示，HPCPCB 是一有效的HDAC 抑制劑，並有進一步作為癌症治療用藥的研究可行性。

Histone deacetylases (HDACs) are potential therapeutic targets for the treatment of hematologic and solid tumor malignancies due to their overexpression 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-((1R,2R)-2-phenylcyclopropanecarboxamido)benzamide (HPCPCB), as a chemotherapeutic drug for solid tumors.First, we examined the cytotoxicity of HPCPCB in various lung and breast cancer cells and their corresponding normal cells using MTT 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 HPCPCB caused cell cycle arrest at G1 phase. Western blotting indicated that proteins required for cell cycle progression such as CDC25A, CDK4 and cyclin E were reduced and the cell cycle inhibitor p21 was up-regulated by HPCPCB treatment. Furthermore, HPCPCB inhibited HDAC activity and induced an increase in acetylated histone proteins H3 and H4 and non-histone proteins p53 and
tubulin. Our findings suggest that HPCPCB is a potent HDAC inhibitor and has potential in cancer treatment.