We reported efficacy of Angelica gigas Nakai (AGN) root ethanol extract and equimolar decursin (D)/decursinol angelate (DA) through daily gavage starting at 8 weeks of age (WOA) to male transgenic adenocarcinoma of mouse prostate (TRAMP) mice such that these modalities suppressed precancerous epithelial lesions in their dorsolateral prostate (DLP) to similar extent, but AGN extract was better than the D/DA mixture at promoting the survival of mice bearing prostate neuroendocrine carcinomas to 28 WOA. Here, we compared by microarray hybridization the mRNA levels in pooled DLP tissues and individual neuroendocrine carcinomas to characterize potential molecular targets of AGN extract and D/DA. Clustering and principal component analyses supported distinct gene expression profiles of TRAMP DLP versus neuroendocrine carcinomas. Pathway Enrichment, Gene Ontology, and Ingenuity Pathway Analyses of differential genes indicated that AGN and D/DA affected chiefly processes of lipid and mitochondrial energy metabolism and oxidation-reduction in TRAMP DLP, while AGN affected neuronal signaling, immune systems and cell cycling in neuroendocrine carcinomas. Protein–Protein Interaction Network analysis predicted and reverse transcription-PCR verified multiple hub genes common in the DLP of AGN- and D/DA-treated TRAMP mice at 28 WOA and select hub genes attributable to the non-D/DA AGN components. The vast majority of hub genes in the AGN-treated neuroendocrine carcinomas differed from those in TRAMP DLP. In summary, the transcriptomic approach illuminated vastly different signaling pathways and networks, cellular processes, and hub genes of two TRAMP prostate malignancy lineages and their associations with the interception efficacy of AGN and D/DA. Prevention Relevance: This study explores potential molecular targets associated with in vivo activity of AGN root alcoholic extract and its major pyranocoumarins to intercept precancerous epithelial lesions and early malignancies of the prostate. Without an ethically-acceptable, clearly defined cancer initiation risk reduction strategy available for the prostate, using natural products like AGN to delay formation of malignant tumors could be a plausible approach for prostate cancer prevention.

中文翻译：

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当归根提取物与吡喃香豆素在 TRAMP 小鼠前列腺早期病变和神经内分泌癌中的拦截靶点


我们报道了当归 (AGN) 根乙醇提取物和等摩尔紫花素 (D)/紫花素醇当归酸酯 (DA) 从 8 周龄 (WOA) 开始每日灌胃对雄性转基因小鼠前列腺腺癌 (TRAMP) 小鼠的功效，使得这些方法以相似的程度抑制背外侧前列腺 (DLP) 的癌前上皮病变，但 AGN 提取物在将患有前列腺神经内分泌癌的小鼠的存活率提高到 28 WOA 方面优于 D/DA 混合物。在这里，我们通过微阵列杂交比较了合并的 DLP 组织和个体神经内分泌癌中的 mRNA 水平，以表征 AGN 提取物和 D/DA 的潜在分子靶标。聚类和主成分分析支持 TRAMP DLP 与神经内分泌癌不同的基因表达谱。差异基因的通路富集、基因本体和独创性通路分析表明，AGN和D/DA主要影响TRAMP DLP中的脂质和线粒体能量代谢和氧化还原过程，而AGN影响神经内分泌中的神经信号、免疫系统和细胞周期。癌。蛋白质-蛋白质相互作用网络分析预测并逆转录 PCR 验证了 28 WOA 时 AGN 和 D/DA 处理的 TRAMP 小鼠 DLP 中常见的多个中心基因，并选择了归因于非 D/DA AGN 成分的中心基因。 AGN 治疗的神经内分泌癌中的绝大多数中心基因与 TRAMP DLP 中的不同。总之，转录组学方法阐明了两种 TRAMP 前列腺恶性肿瘤谱系截然不同的信号通路和网络、细胞过程和中心基因及其与 AGN 和 D/DA 拦截功效的关联。 预防相关性：本研究探讨了与 AGN 根醇提取物及其主要吡喃香豆素体内活性相关的潜在分子靶标，以拦截前列腺癌前上皮病变和早期恶性肿瘤。如果没有伦理上可接受的、明确定义的前列腺癌症发生风险降低策略，使用 AGN 等天然产品来延缓恶性肿瘤的形成可能是预防前列腺癌的一种可行方法。