Tang Wen-jian, Yang Yong-an, Xu He, Shi Jing-bo, Liu Xin-hua
School of Pharmacy, Anhui Medical University, Hefei, 230032, P. R. China.
Sci Rep. 2014 Nov 19;4:7106. doi: 10.1038/srep07106.
Glycyrrhizic acid (GA) is a natural product with favorable antitumor activity. But, glycyrrhetinic acid monoglucuronide (GAMG) showed stronger antitumor activity than GA. It is of our interest to generate and identify novel compounds with regulation telomerase for cancer therapy. So, in this study, 18α-GAMG was synthesized via biotransformation. In vitro studies showed that it displayed potent anticancer activity and high selectivity on tumor liver cell SMMC-7721 versus human normal liver cell L-02. The further results in vivo confirmed that it could significantly improve pathological changes of N,N-diethylnitrosamine (DEN)-induced rat hepatic tumor. Western blot and immunofluorescence results indicated that the expression of p65-telomerase reverse transcriptase (TERT) was clearly down-regulated treated with it. Taken together, this study for the first time identified an active compound with high selectivity on tumor liver cell in mice. Furthermore, the title compound could inhibit the expression of protein p65 and TERT. These data support further studies to assess the rational design of more efficient p65 modulators in the future.
甘草酸（GA）是一种具有良好抗肿瘤活性的天然产物。但是，甘草次酸单葡萄糖醛酸苷（GAMG）显示出比GA更强的抗肿瘤活性。生成并鉴定具有调节端粒酶作用的新型化合物用于癌症治疗是我们感兴趣的。因此，在本研究中，通过生物转化合成了18α-GAMG。体外研究表明，它对肿瘤肝癌细胞SMMC-7721相对于人正常肝细胞L-02表现出强大的抗癌活性和高选择性。体内进一步结果证实，它可以显著改善N，N-二乙基亚硝胺（DEN）诱导的大鼠肝肿瘤的病理变化。蛋白质印迹和免疫荧光结果表明，用其处理后p65-端粒酶逆转录酶（TERT）的表达明显下调。综上所述，本研究首次鉴定出一种对小鼠肿瘤肝癌细胞具有高选择性的活性化合物。此外，标题化合物可以抑制蛋白质p65和TERT的表达。这些数据支持未来进一步研究以评估更有效p65调节剂的合理设计。
