Selective toxicity of glycyrrhetinic acid against tumorigenic r/m HM-SFME-1 cells is potentially attributed to downregulation of glutathione.
Selective toxicity of glycyrrhetinic acid against tumorigenic r/m HM-SFME-1 cells is potentially attributed to downregulation of glutathione.
复制标题
DOI：
10.1016/j.biochi.2011.04.011
复制
发表时间：
2011-07
期刊：
影响因子：
3.9
通讯作者：
H. Yamaguchi;T. Yu;Y. Kidachi;T. Akitaya;K. Yoshida;K. Kamiie;T. Noshita;H. Umetsu;K. Ryoyama
中科院分区：
文献类型：
--
作者：
H. Yamaguchi;T. Yu;Y. Kidachi;T. Akitaya;K. Yoshida;K. Kamiie;T. Noshita;H. Umetsu;K. Ryoyama
从植物中提取的天然产物有望在创造新的、安全的、改进的化学预防和治疗抗肿瘤药物方面发挥重要作用。选择性也是癌症预防和治疗中的一个重要问题。本研究旨在扩展我们之前关于甘草成分甘草次酸（GA）对c-Ha-ras和c-myc诱导的肿瘤细胞选择性抗增殖作用的研究。硅配体-受体对接模拟显示，GA作为11β-羟基类固醇脱氢酶2型抑制剂。GA通过上调活性氧和下调谷胱甘肽（GSH）来破坏肿瘤细胞的氧化还原平衡。GSH抑制剂l-丁硫氨酸-[S， R]-亚砜亚胺增强了ga诱导的GSH还原和细胞毒性。n -乙酰-l-半胱氨酸是一种抗氧化剂和GSH的前体，可以恢复ga诱导的肿瘤细胞中GSH的减少和细胞毒性。综上所述，这些数据强调了GA对GSH的下调以及GSH在改善GA介导的细胞毒性方面的功效，支持了GSH参与GA对肿瘤细胞的选择性毒性的观点。
Natural products from plants are expected to play significant roles in creating new, safe and improved chemopreventive and therapeutic antitumor agents. Selectivity is also an important issue in cancer prevention and therapy. The present study was designed to extend our previous study on the c-Ha-ras and c-myc-induced tumor cell-selective antiproliferative effects of a licorice component, glycyrrhetinic acid (GA). An in silico ligand-receptor docking simulation revealed that GA acts as an 11β-hydroxysteroid dehydrogenase type 2 inhibitor. GA disrupted the redox balance in tumor cells through upregulation of reactive oxygen species and downregulation of glutathione (GSH). The GA-induced GSH reduction and cytotoxicity were enhanced by an inhibitor of GSH, l-buthionine-[S, R]-sulfoximine. N-acetyl-l-cysteine, an antioxidant and precursor of GSH, restored the GA-induced GSH reduction and cytotoxicity in tumor cells. Taken together, these data highlighting the downregulation of GSH by GA and the efficacy of GSH in ameliorating GA-mediated cytotoxicity support the notion that GSH is involved in the selective toxicity of GA toward tumor cells.