Licochalcone A, a natural chalconoid isolated from Glycyrrhiza inflata root, induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell carcinoma
Licochalcone A, a natural chalconoid isolated from Glycyrrhiza inflata root, induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell carcinoma
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DOI：
10.3892/ijo.2014.2461
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发表时间：
2014-08-01
影响因子：
5.2
通讯作者：
Shim, Jung-Hyun
中科院分区：
文献类型：
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作者：
Cho, Jung Jae;Chae, Jung-Il;Shim, Jung-Hyun
甘草酮A(LCA)是从甘草根中提取的一种查尔酮类化合物，具有广泛的生物学功能，如抗肿瘤、抗血管生成、抗寄生虫、抗氧化、抗菌和抗炎等。然而，LCA对口腔鳞状细胞癌(OSCC)的抗癌作用尚未见报道。我们的数据显示LCA以浓度和时间依赖的方式抑制OSCC细胞(HN22和HSC4)的生长。从机制上讲，它是通过下调特异性蛋白1(Sp1)的表达以及随后调节Sp1下游蛋白如p27、p21、细胞周期蛋白D1、Mcl-1和Survivin来实现的。在此，我们发现LCA诱导HSC4和HN22细胞的凋亡，表现为亚G(1)群、核固缩、Annexin V染色、多caspase活性和凋亡调节蛋白Bax、Bid、Bc1-(Xl)、caspase-3和ParR。因此，本研究强烈提示LCA通过下调Sp1的表达诱导口腔鳞状细胞癌细胞凋亡，提示其可能用于治疗人OS CC。
Licochalcone A (LCA), a chalconoid derived from root of Glycyrrhiza inflata, has been known to possess a wide range of biological functions such as antitumor, anti-angiogenesis, antiparasitic, anti-oxidant, antibacterial and anti-inflammatory effects. However, the anticancer effects of LCA on oral squamous cell carcinoma (OSCC) have not been reported. Our data showed that LCA inhibited OSCC cell (HN22 and HSC4) growth in a concentration- and time-dependent manner. Mechanistically, it was mediated via downregulation of specificity protein 1 (Sp1) expression and subsequent regulation of Sp1 downstream proteins such as p27, p21, cyclin D1, Mcl-1 and survivin. Here, we found that LCA caused apoptotic cell death in HSC4 and HN22 cells, as characterized by sub-G(1) population, nuclear condensation, Annexin V staining, and multi-caspase activity and apoptotic regulatory proteins such as Bax, Bid, Bc1-(xl), caspase-3 and PARR Consequently, this study strongly suggests that LCA induces apoptotic cell death of OSCC cells via downregulation of Sp1 expression, prompting its potential use for the treatment of human OS CC.