費氏麴菌二次代謝物對人類大腸直腸癌細胞株之影響

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Title:	費氏麴菌二次代謝物對人類大腸直腸癌細胞株之影響 Effects of secondary metabolites from Neosartorya fischeri on human colorectal adenocarcinoma cell line
Authors:	葉昱彤
Contributors:	生物科技系田乃月劉坤湘
Keywords:	費氏麴菌乙醯基環帶麴菌素人類大腸直腸癌微陣列分析即時定量聚合酶鏈鎖反應 p53路徑 acetylaszonalenin Neosartorya fischeri human colorectal adenocarcinoma cells microarray analysis quantitative real-time polymerase chain reaction p53 signaling pathway
Date:	2018
Issue Date:	2019-02-27 16:49:24 (UTC+8)
Abstract:	絲狀真菌具有產生多樣結構與各種生物活性的二次代謝物之能力，如抗細菌、抗真菌及抗腫瘤等生物活性，應用在生物技術、食品加工和醫藥化學等領域。費氏麴菌在分類學上屬於新薩托屬，是一種嗜熱菌，被發現存在於潮濕土壤中，是導致水果腐敗的原因之一。費氏麴菌主要二次代謝物為乙醯基環帶麴菌素，由ana基因叢集所表現的anaPS、anaAT與anaPT三種酵素催化產生，但有關於乙醯基環帶麴菌素生物活性的相關文獻則相當稀少。由於乙醯基環帶麴菌素生合成路徑的中間產物具有抗腫瘤活性，因此合理推測乙醯基環帶麴菌素可能具有類似或是新的生物活性。為驗證乙醯基環帶麴菌素的抗腫瘤活性，本研究選擇我國國人罹患率甚高的人類大腸直腸癌，以細胞株模式做為抗腫瘤試驗對象。本研究首先以優化培養條件使費氏麴菌產生出較多的乙醯基環帶麴菌素，自發酵液純化出該化合物，以不同濃度進行細胞毒性測試，發現其具有毒殺人類大腸直腸癌細胞的活性。以人類全基因體晶片進行微陣列分析，結果發現可能主要經由p53路徑造成毒殺癌細胞。再以即時定量聚合酶鏈鎖反應針對p53路徑數個目標基因分析表現情形，發現ATM、p53、caspase-8與caspase-3基因表現增加，CHK2基因表現下降，此結果提供未來深入了解乙醯基環帶麴菌素的分子作用機制，以期未來可應用於抗癌藥物的開發。 Filamentous fungi produce secondary metabolites with distinct structures and various biological activities for a wide range in biotechnology, food, and medical fields such as antibacterial, antifungal, and antitumor activity and used in different fields. Neosartorya fischeri is a heat-resistant mold frequently reported to cause spoilage in fruit products. Acetylaszonalenin is found to be the major secondary metabolite in N. fischeri, and catalyzed by anaPS, anaPT as well as anaAT encoded by a putative acetylaszonalenin-biosynthetic gene cluster. Even though this gene cluster was identified in N. fischeri, no reports on bioactivities of acetylaszonalenin could be found until now. Cause the precursor, benzodiazepinedione of acetylaszonalenin biosynthetic pathway whose antitumor activity was verified, we conjecture that acetylaszonalenin might have antitumor activity. To elucidate the antitumor activity of acetylaszonalenin, we used human colorectal adenocarcinoma cells as antitumor test object. We performed cell viability assay with various concentrations of acetylaszonalenin purified from mycelial liquid culture of N. fischeri. The results indicated that there is cytotoxicity when human colorectal adenocarcinoma cells were tested after 24- , 48- and 72-hour treatments. To better understand the molecular mechanisms involved in the response of human colorectal adenocarcinoma cells to acetylaszonalenin, microarray analysis was used to help identify significantly expressed genes that may contribute to the response. After obtaining a large-scale survey of the variations in gene expression patterns and gene ontology enrichment analysis, the p53 signaling pathway would be the first pathway to be clarified at present. These results could provide insight information into the molecular mechanisms of the antitumor activity of acetylaszonalenin.
Relation:	電子全文公開日期：2023-09-10，學年度：106， 67頁
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Dissertations and Theses

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