Hsia Shih-Min, Yu Cheng-Chia, Shih Yin-Hua, Yuanchien Chen Michael, Wang Tong-Hong, Huang Yu-Ting, Shieh Tzong-Ming
School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan.
Institute of Oral Science, School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
Head Neck. 2016 Apr;38 Suppl 1:E360-71. doi: 10.1002/hed.24001. Epub 2015 Jun 16.
Isoliquiritigenin (ISL), a natural compound extracted from licorice, has chemopreventive and antitumor activities. The purpose of this study was to investigate the anticancer effect of ISL on human oral squamous cell carcinoma (OSCC).
The anti-OSCC effects of ISL were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test, flow cytometry, reverse transcription-polymerase chain reaction, Western blotting, promoter activity, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, malignant phenotype analysis, microRNA, and xenografting.
ISL induced OSCC cell cycle G2/M phase arrest, apoptosis, and DNA damage. However, the DNA repair-associated ataxia telangiectasia mutated (ATM) and phospho-ATM were downregulated, ATM mRNA remained unchanged, and the downstream signals were inhibited. ATM recovered when the caspase activity was blocked by Z-DVED-FMK. A low dose of ISL inhibited OSCC malignancy in vitro and reduced the tumor size in vivo.
ATM was cleaved by ISL-activated caspase, thus inhibiting DNA repair in OSCC cells. Therefore, ISL is a promising chemopreventive agent against oral cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E360-E371, 2016.
异甘草素（ISL）是从甘草中提取的一种天然化合物，具有化学预防和抗肿瘤活性。本研究旨在探讨ISL对人口腔鳞状细胞癌（OSCC）的抗癌作用。
采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐试验、流式细胞术、逆转录-聚合酶链反应、蛋白质印迹法、启动子活性检测、末端脱氧核苷酸转移酶dUTP缺口末端标记法、恶性表型分析、微小RNA检测和异种移植等方法评估ISL对OSCC的作用。
ISL诱导OSCC细胞周期G2/M期阻滞、凋亡和DNA损伤。然而，与DNA修复相关的共济失调毛细血管扩张突变（ATM）和磷酸化ATM表达下调，ATM mRNA水平不变，其下游信号受到抑制。当半胱天冬酶活性被Z-DVED-FMK阻断时，ATM恢复。低剂量的ISL在体外抑制OSCC恶性程度，在体内减小肿瘤大小。
ISL激活的半胱天冬酶可切割ATM，从而抑制OSCC细胞中的DNA修复。因此，ISL是一种有前景的口腔癌化学预防剂。© 2015威利期刊公司。头颈外科38: E360-E371, 2016。
