2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38549Recent studies find that histone acetylation plays an important role in eukaryotic gene trnascription, carcinogenesis and the therapy of cancer. Histon acetyl transferase (HAT) and histon deaetylase (HDAC) are enzymes involved in the remodeling of chromatin, and have a key role in the epigenetic regulation of gene expression. Generally, histone acetylation contributes to the formaiton of a transcriptionally competent environment by 「opening」 chromatin and permits access of transcription factors to DNA,whereas, histone deacetylation contributes to a 「closed」chromatin state and transcriptional repression. The histon acetylation-deacetylation balance that maintained through HAT and HDAC enzyme actitives favors hypoacetylation in tumor cells. In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer. The flavonoids are polycyclic structures containing two aromatic rings (A and B) linked by a heterocyclic ring C. They universally present as constituents of plants such as vegetable, fruits and several plants for traditional medicine of Asia. Many studies report that the flavonoids has a variety of anticancer effects such as cell growth and kinase activity inhibition, apoptosis induction, suppression of the secretion of matrix metalloproteinases and of tumor angiogenesis and invasive behavior. The mechanisms have been widely research on the related between flavonoids and anticancer effect. However, whether the flavonoids have the chromatin remodeling activity mediated by histon acetylation and to regulate gene expression await further elucidation. More than 5000 different flavonoids have been described. In accordance with there structure can be separate to six major subclasses of flavonoids include the flavones, flavonols, flavanones, catechins or flavanols, anthocyanidins, and isoflavones. It is indicated that C2-C3 double bond of flavonoid exhibit potent anti-cancer potential such as quercetin which is a flavonol. Thereafter, we will first evaluate the anticancer potential of quercetin and analysis its effect on regulation gene expression mediated by acetylation modification of histon in leukemia and solid tumor cells respectively. Then we will elucidate the structure relationship of flavonoid on anticancer potential and the chromatin remodeling effect. The following subjects will be evaluated: 1. The first years (1) The effect of quercetin on proliferation, apoptosis, migration and invasion of leukemia cancer cell. (2) The effect of quercetin on gene expression that associated with leukemia cancer cells proliferation, apoptosis, migration and invasion. (3) The effect of quercetin on HATs and HDACs activity. (4) The effect of quercetin on different chromatin remodelling cofactors recruited on the specific gene promoter. 2. The second years (1) The effect of quercetin on proliferation, apoptosis, migration and invasion of solid tumor cancer cell (such as hepatoma and breast cancer cells). (2) The effect of quercetin on gene expression that associated with solid tumor cancer cell proliferation, apoptosis, migration and invasion. (3) The effect of quercetin on HATs and HDACs activity of solid tumor cancer cell. (4) The effect of quercetin on different chromatin remodelling cofactors recruited on the specific gene promoter of solid tumor cancer cell. 3. The third years (1) Screening the effect of flavonoids on cancer cells proliferation, apoptosis, migration and invasion. (2) The effect of flavonoids on gene expression that associated with cancer cells proliferation, apoptosis, migration and invasion. (3) Structure evaluation of flavonoids on HATs and HDACs activity.癌症是一種基因突變或異常的疾病，近年來研究證實透過遺傳修飾的改變 (epigenetic changes)造成染色體重組(remodelling of chromatin)來調控基因的表 現，在癌症的形成與發展也扮演著關鍵性的角色。組蛋白去乙醯基.（HDACs） 與組蛋白乙醯基轉移.（HATs）是染色體重組的重要酵素，近幾年的研究顯示， 抑制HDACs 可恢復與癌症相關的不正常遺傳變異，各種組蛋白去乙醯基.抑制 劑（HDACi）的研究也被發現具有強而有力且專一性的抗癌活性。因此改變組蛋 白乙醯化狀態進而造成染色體重組來調控基因的表現是一個有發展潛力的抗癌 策略. 類黃酮是一種多酚類的化合物，其結構包括二個芳香環(A, B)由一個異環(C) 連結，廣泛的存在於蔬菜、水果及藥用植物中，數千年來在亞洲國家所使用的一 些傳統藥用的植物及香料，也常含有類黃酮的衍生物，許多關於類黃酮對癌細胞 的研究報告，顯示類黃酮具有各種的抗癌作用，包括抑制細胞生長、抑制激.活 性、誘導細胞凋亡、抑制MMPs 的分泌以及血管新生與腫瘤的侵犯的能力，對於 類黃酮抗癌作用的相關機制也多有研究，然而對於類黃酮是否具有染色體重組的 活性以及是否可透過染色體的重組調控基因的表現，達到抗癌的目的還有待進一 步的研究。 目前已有超過5000 種的類黃酮衍生物被發現，依據其結構上的差異主要可區 分為六種包括: flavones, flavanones, flavanols, flavonols, isoflavones, anthocyanidins, 其中文獻指出結構中連接異環為不飽和者如類黃醇(flavanols) 、類黃素(flavones) 有較強之抗癌活性，檞黃素(quercetin)即為一種類黃醇，故本研究擬先分析檞黃素 對各種癌細胞之抗癌活性及其對癌細胞組蛋白乙醯化改變所調控基因的表現影響 及其分子機制，進而探討類黃酮結構與抗癌活性及對癌細胞組蛋白乙醯化改變所 調控基因的表現影響之相關性。主要研究項目如下: 第一年: 檞黃素對血癌細胞之作用研究 1. 觀測檞黃素對血癌細胞生長、凋亡、血管新生、轉移及侵犯作用之影響。 2. 觀測檞黃素對血癌細胞生長、凋亡、血管新生、轉移及侵犯作用有關分子基 因表現之影響。 3. 觀測檞黃素對血癌細胞HATs 與HDACs 表現及活性之影響。 4. 觀測檞黃素對血癌細胞染色體重組相關蛋白與基因promoter 結合之影響。 第二年: 檞黃素對固態腫瘤細胞之作用研究 1. 測試檞黃素對如肺癌、肝癌、乳癌、攝護腺癌等固態腫瘤細胞株之作用，選 則作用強之一株細胞株進行以下研究。 2. 觀測檞黃素對癌細胞生長、凋亡、血管新生、轉移及侵犯作用之影響。 3. 觀測檞黃素對癌細胞生長、凋亡、血管新生、轉移及侵犯作用有關分子基因 表現之影響。 4. 觀測檞黃素對癌細胞HATs 與HDACs 表現及活性之影響。 5. 觀測檞黃素對癌細胞染色體重組相關蛋白與基因promoter 結合之影響。 第三年: 類黃酮衍生物結構與抗癌活性及對癌細胞染色體重組調控基因的表現影響研 究 1. 取六種結構不同類黃酮衍生物對血癌細胞株及一固態腫瘤細胞株進行抗癌活性 測試與比較。 2. 觀測六種結構不同類黃酮衍生物對癌細胞生長、凋亡、血管新生、轉移及侵犯 作用有關分子基因表現之影響。 3. 觀測六種結構不同類黃酮衍生物對癌細胞HATs 與HDACs 表現及活性之影響。 建立結構與活性相關性。檞黃素組蛋白去乙醯基組蛋白乙醯基轉移類黃酮抗癌flavonoidquercetinHDACHATaiticancerProject