State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, P. R. China.
Food Funct. 2018 Dec 13;9(12):6517-6525. doi: 10.1039/c8fo02079e.
To enhance production of Antrodia cinnamomea triterpenoids (ACTs) from mycelia in solid-state culture, α-terpineol was added to the medium as an elicitor at an optimal concentration of 0.05 mL L-1. Multi-stage solvent extraction and HPLC analysis were performed, and the compositions of ACTs-E (from culture with elicitor) and ACTs-NE (from culture without elicitor) were found to be quite different. In assays of in vitro antitumor activity, ACTs-E, in comparison with ACTs-NE, produced stronger viability reduction in several tumor cell lines and stronger apoptosis induction in HeLa in a dose-dependent manner. Several related proteins involved in the mitochondrial pathway of apoptosis (p53, Bax, caspase-3) did not show expression upregulation by ACTs-E, suggesting that apoptosis induction occurred through a p53-independent process. Further analysis revealed that ACTs-E strongly inhibited synthesis of topoisomerase I (TOP1) and tyrosyl-DNA phosphodiesterase I (TDP1), which are involved in DNA repair, at both transcriptional and protein levels. Our findings suggest that ACTs-E have potential for applications in the pharmaceutical, clinical, and functional food industries, as a novel antitumor agent and a dual TOP1/TDP1 inhibitor.
为了提高固态培养菌丝体中樟芝三萜类化合物（ACTs）的产量，将α-松油醇作为诱导剂添加到培养基中，最佳浓度为 0.05 mL L-1。进行了多步溶剂萃取和 HPLC 分析，发现用诱导剂处理的 ACTs-E 和未用诱导剂处理的 ACTs-NE 的组成差异很大。在体外抗肿瘤活性测定中，与 ACTs-NE 相比，ACTs-E 以剂量依赖性方式在几种肿瘤细胞系中产生更强的细胞活力降低和更强的 HeLa 细胞凋亡诱导作用。几种与线粒体凋亡途径相关的蛋白（p53、Bax、caspase-3）没有被 ACTs-E 上调表达，表明凋亡诱导是通过 p53 非依赖性途径发生的。进一步分析表明，ACTs-E 强烈抑制拓扑异构酶 I（TOP1）和酪氨酸-DNA 磷酸二酯酶 I（TDP1）的合成，这两种酶参与 DNA 修复，在转录和蛋白质水平上均受到抑制。我们的研究结果表明，ACTs-E 具有作为新型抗肿瘤剂和 TOP1/TDP1 双重抑制剂在制药、临床和功能性食品行业中的应用潜力。
