Licochalcone-A induces intrinsic and extrinsic apoptosis via ERK1/2 and p38 phosphorylation-mediated TRAIL expression in head and neck squamous carcinoma FaDu cells.
Licochalcone-A induces intrinsic and extrinsic apoptosis via ERK1/2 and p38 phosphorylation-mediated TRAIL expression in head and neck squamous carcinoma FaDu cells.
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DOI：
10.1016/j.fct.2014.12.013
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发表时间：
2015-03
期刊：
影响因子：
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通讯作者：
Kim JS
中科院分区：
文献类型：
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作者：
Park MR;Kim SG;Cho IA;Oh D;Kang KR;Lee SY;Moon SM;Cho SS;Yoon G;Kim CS;Oh JS;You JS;Kim DK;Seo YS;Im HJ;Kim JS
我们研究了甘草酮-A(LICO-A)诱导咽鳞癌FaDu细胞株的凋亡及其活性的途径。从甘草根中提纯的LICO-A具有细胞毒作用，可显著增加FaDu细胞的死亡。通过细胞活力测定，我们确定了LiCo-A对FaDu细胞的IC50值约为100µM。在经LiCo-A处理24小时的FaDu细胞中，观察到染色质凝集，与此结果一致，当FaDu细胞被LiCo-A处理时，凋亡细胞数呈时间依赖性地增加。LICO-A处理的FaDu细胞TRAIL表达显著上调，且呈剂量依赖关系。随后，caspase和PARP聚合酶等凋亡因子以caspase依赖的方式被激活。此外，在接受LICO-A治疗后，促凋亡因子水平显著升高，而抗凋亡因子水平下降。LICO-A诱导的TRAIL表达部分由涉及ERK1/2和p38的MAPK信号通路介导。最后，在体内异种移植小鼠模型中，LICO-A通过激活caspase-3有效地抑制了FaDu细胞异种移植瘤的生长，而不影响小鼠的体重。综上所述，这些数据表明，LICO-A具有潜在的化学预防作用，因此应该被开发为咽鳞癌的化疗药物。
We investigated Licochalcone-A (Lico-A)-induced apoptosis and the pathway underlying its activity in a pharyngeal squamous carcinoma FaDu cell line. Lico-A purified from root of Glycyrrhiza inflata had cytotoxic effects, significantly increasing cell death in FaDu cells. Using a cell viability assay, we determined that the IC50 value of Lico-A in FaDu cells was approximately 100 µM. Chromatin condensation was observed in FaDu cells treated with Lico-A for 24 h. Consistent with this finding, the number of apoptotic cells increased in a time-dependent manner when FaDu cells were treated with Lico-A. TRAIL was significantly up-regulated in Lico-A-treated FaDu cells in a dose-dependent manner. Apoptotic factors such as caspases and PARP polymerase were subsequently activated in a caspase-dependent manner. In addition, levels of pro-apoptotic factors increased significantly in response to Lico-A treatment, while levels of anti-apoptotic factors decreased. Lico-A-induced TRAIL expression was mediated in part by a MAPK signaling pathway involving ERK1/2 and p38. Lastly, in an in vivo xenograft mouse model, Lico-A treatment effectively suppressed the growth of FaDu cell xenografts by activating caspase-3, without affecting the body weight of mice. Taken together, these data suggest that Lico-A has potential chemopreventive effects and should therefore be developed as a chemotherapeutic agent for pharyngeal squamous carcinoma.