A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is unknown. Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays. Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity. In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity.

中文翻译：

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氧化叶农杆菌及其生物活性成分Nootkatone在结直肠癌细胞中的抗增殖活性。

已知叶青曲霉提取物具有广泛的药理活性。但是，尚不清楚叶青曲霉及其生物活性化合物Nootkatone在大肠癌中的分子机制。我们的研究旨在通过多种体外试验来研究叶绿假单胞菌及其生物活性化合物Nootkatone在抑制肿瘤中的作用。氧化叶农杆菌提取物和Nootkatone在大肠癌细胞中均表现出抗增殖活性。氧化叶农杆菌在大肠癌细胞中表现出抗氧化活性，可能是通过诱导HO-1介导的。此外，在存在叶氧假单胞菌的情况下，促凋亡蛋白NAG-1和细胞增殖蛋白细胞周期蛋白D1的表达分别增加和减少。当检查抗癌活性时，Nootkatone处理可导致菌落和球体形成减少。相应地，Nootkatone也导致NAG-1表达增加和cyclin D1表达减少。Nootkatone抑制细胞周期蛋白D1的机制涉及蛋白质水平调节，而Nootkatone在转录水平上增加NAG-1表达。除了具有PPARγ结合活性外，Nootkatone还可以提高EGR-1表达，从而最终增强NAG-1启动子活性。总之，我们的发现表明，Nootkatone是一种具有抗增殖和促凋亡活性的抗肿瘤化合物。除具有PPARγ结合活性外，Nootkatone还提高EGR-1表达，最终导致NAG-1启动子活性增强。总之，我们的发现表明，Nootkatone是一种具有抗增殖和促凋亡活性的抗肿瘤化合物。除具有PPARγ结合活性外，Nootkatone还提高EGR-1表达，最终导致NAG-1启动子活性增强。总之，我们的发现表明，Nootkatone是一种具有抗增殖和促凋亡活性的抗肿瘤化合物。