Isoliquiritigenin as a cause of DNA damage and inhibitor of ataxia-telangiectasia mutated expression leading to G2/M phase arrest and apoptosis in oral squamous cell carcinoma

Background 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). Methods The anti‐OSCC effects of ISL were evaluated us...

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Published in:Head & neck 2016-04, Vol.38 (S1), p.E360-E371
Main Authors: Hsia, Shih-Min, Yu, Cheng-Chia, Shih, Yin-Hua, Yuanchien Chen, Michael, Wang, Tong-Hong, Huang, Yu-Ting, Shieh, Tzong-Ming
Format: Article
Language:English
Subjects:
Apoptosis
ataxia telangiectasia mutated (ATM)
Ataxia Telangiectasia Mutated Proteins - genetics
Ataxia Telangiectasia Mutated Proteins - metabolism
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - pathology
Cell Cycle Checkpoints - drug effects
Cell Division
Cell Line, Tumor
Chalcones - pharmacology
DNA Damage
Glycyrrhiza glabra
Humans
isoliquiritigenin
Mouth Neoplasms - drug therapy
Mouth Neoplasms - pathology
oral squamous cell carcinoma (OSCC)
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Summary:Background 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). Methods 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. Results 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. Conclusion 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
ISSN:1043-3074
1097-0347
DOI:10.1002/hed.24001