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

Shih Min Hsia, Cheng Chia Yu, Yin Hua Shih, Michael Yuanchien Chen, Tong Hong Wang, Yu Ting Huang, Tzong Ming Shieh

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalHead and Neck
DOIs
Publication statusPublished - 2016

Fingerprint

Ataxia Telangiectasia
G2 Phase
Cell Division
DNA Damage
Squamous Cell Carcinoma
Apoptosis
Caspases
DNA Repair
Glycyrrhiza
Heterologous Transplantation
DNA Nucleotidylexotransferase
Mouth Neoplasms
isoliquiritigenin
MicroRNAs
Reverse Transcription
Neoplasms
Cell Cycle
Flow Cytometry
Down-Regulation
Western Blotting

Keywords

  • Apoptosis
  • Ataxia telangiectasia mutated (ATM)
  • DNA damage
  • Isoliquiritigenin
  • Oral squamous cell carcinoma (OSCC)

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

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. / Hsia, Shih Min; Yu, Cheng Chia; Shih, Yin Hua; Yuanchien Chen, Michael; Wang, Tong Hong; Huang, Yu Ting; Shieh, Tzong Ming.

In: Head and Neck, 2016.

Research output: Contribution to journalArticle

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abstract = "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.",
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T1 - 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

AU - Hsia, Shih Min

AU - Yu, Cheng Chia

AU - Shih, Yin Hua

AU - Yuanchien Chen, Michael

AU - Wang, Tong Hong

AU - Huang, Yu Ting

AU - Shieh, Tzong Ming

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Ataxia telangiectasia mutated (ATM)

KW - DNA damage

KW - Isoliquiritigenin

KW - Oral squamous cell carcinoma (OSCC)

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