3-Hydroxyanthranic acid inhibits growth of oral squamous carcinoma cells through growth arrest and DNA damage inducible alpha
Objectives: The specific role of 3-hydroxyanthranilic acid(3-HAA) in oral squamous cell carcinoma (OSCC) remains unclear. This study investigated the roles of 3-HAA in OSCC and the underlying mechanism. Materials and methods: The effects of 3-HAA on OSCC were examined using CCK-8, colony formation,...
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| Format: | Article |
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Elsevier
2025-02-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000099 |
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| author | Guifang Gan Xinxia Zhou Qiaoping Zheng Xianfu Gao Xu Chen Han Zhang Jinghao Liu Zhaopeng Shi Fuxiang Chen |
| author_facet | Guifang Gan Xinxia Zhou Qiaoping Zheng Xianfu Gao Xu Chen Han Zhang Jinghao Liu Zhaopeng Shi Fuxiang Chen |
| author_sort | Guifang Gan |
| collection | DOAJ |
| description | Objectives: The specific role of 3-hydroxyanthranilic acid(3-HAA) in oral squamous cell carcinoma (OSCC) remains unclear. This study investigated the roles of 3-HAA in OSCC and the underlying mechanism. Materials and methods: The effects of 3-HAA on OSCC were examined using CCK-8, colony formation, EdU incorporation assays and xenograft mouse model. The underlying mechanisms were investigated with RNA-seq, apoptosis array and cell cycle array. Short hairpin RNAs (shRNAs) were used to knockdown the expression of growth arrest and DNA damage inducible alpha (GADD45A) in OSCC cells. CCK-8 and xenograft mouse model were employed to elucidate the role of GADD45A. The binding sites between GADD45A and Yin Yang 1(YY1) were determined using luciferase reporter assay. Results: 3-HAA was selectively down-regulated in OSCC patients and the decreasing level intensified with pathological progression. Higher expression of kynurenine 3-monooxygenase (KMO) and kynureninase (KYNU), which can increase the content of 3-HAA, was associated with poorer prognosis of OSCC patients. Exogenous 3-HAA hampered growth of OSCC cells both in vitro and in vivo. 3-HAA induced growth arrest, G2/M-phase arrest, and apoptosis of OSCC cells. RNA-seq indicated that 3-HAA significantly increased GADD45A expression. 3-HAA promoted transcription of GADD45A by transcription factor YY1. Knockdown of GADD45A significantly reversed 3-HAA-induced growth inhibition of OSCC cells in vivo and in vitro. Discussion: 3-HAA induced apoptosis and cell cycle arrest of OSCC cells via GADD45A, indicating that 3-HAA and GADD45A are potential therapeutic targets for OSCC. |
| format | Article |
| id | doaj-art-5756eebe79004712bdeeaeb682616898 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-5756eebe79004712bdeeaeb6826168982025-01-22T05:41:36ZengElsevierTranslational Oncology1936-52332025-02-01521022783-Hydroxyanthranic acid inhibits growth of oral squamous carcinoma cells through growth arrest and DNA damage inducible alphaGuifang Gan0Xinxia Zhou1Qiaoping Zheng2Xianfu Gao3Xu Chen4Han Zhang5Jinghao Liu6Zhaopeng Shi7Fuxiang Chen8Shanghai Ninth People's Hospital, Department of Clinical Laboratory medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China; College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR ChinaShanghai Ninth People's Hospital, Department of Clinical Laboratory medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR ChinaShanghai Ninth People's Hospital, Department of Clinical Laboratory medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR ChinaShanghai Profleader Biotech Co., Ltd., Shanghai 200003, PR ChinaShanghai Ninth People's Hospital, Department of Clinical Laboratory medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR ChinaShanghai Ninth People's Hospital, Department of Clinical Laboratory medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR ChinaShanghai Ninth People's Hospital, Department of Clinical Laboratory medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR ChinaDepartment of Histoembryology, Genetics and Developmental Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China; Correspondence author at: Department of Histoembryology, Genetics and Developmental Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.Shanghai Ninth People's Hospital, Department of Clinical Laboratory medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, PR China; College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China; Correspondence author at: Department of Clinical Immunology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, PR China.Objectives: The specific role of 3-hydroxyanthranilic acid(3-HAA) in oral squamous cell carcinoma (OSCC) remains unclear. This study investigated the roles of 3-HAA in OSCC and the underlying mechanism. Materials and methods: The effects of 3-HAA on OSCC were examined using CCK-8, colony formation, EdU incorporation assays and xenograft mouse model. The underlying mechanisms were investigated with RNA-seq, apoptosis array and cell cycle array. Short hairpin RNAs (shRNAs) were used to knockdown the expression of growth arrest and DNA damage inducible alpha (GADD45A) in OSCC cells. CCK-8 and xenograft mouse model were employed to elucidate the role of GADD45A. The binding sites between GADD45A and Yin Yang 1(YY1) were determined using luciferase reporter assay. Results: 3-HAA was selectively down-regulated in OSCC patients and the decreasing level intensified with pathological progression. Higher expression of kynurenine 3-monooxygenase (KMO) and kynureninase (KYNU), which can increase the content of 3-HAA, was associated with poorer prognosis of OSCC patients. Exogenous 3-HAA hampered growth of OSCC cells both in vitro and in vivo. 3-HAA induced growth arrest, G2/M-phase arrest, and apoptosis of OSCC cells. RNA-seq indicated that 3-HAA significantly increased GADD45A expression. 3-HAA promoted transcription of GADD45A by transcription factor YY1. Knockdown of GADD45A significantly reversed 3-HAA-induced growth inhibition of OSCC cells in vivo and in vitro. Discussion: 3-HAA induced apoptosis and cell cycle arrest of OSCC cells via GADD45A, indicating that 3-HAA and GADD45A are potential therapeutic targets for OSCC.http://www.sciencedirect.com/science/article/pii/S19365233250000993-hydroxyanthranilc acidOral squamous cell carcinomaGrowth arrest and DNA damage inducible alphatumor proliferation |
| spellingShingle | Guifang Gan Xinxia Zhou Qiaoping Zheng Xianfu Gao Xu Chen Han Zhang Jinghao Liu Zhaopeng Shi Fuxiang Chen 3-Hydroxyanthranic acid inhibits growth of oral squamous carcinoma cells through growth arrest and DNA damage inducible alpha Translational Oncology 3-hydroxyanthranilc acid Oral squamous cell carcinoma Growth arrest and DNA damage inducible alpha tumor proliferation |
| title | 3-Hydroxyanthranic acid inhibits growth of oral squamous carcinoma cells through growth arrest and DNA damage inducible alpha |
| title_full | 3-Hydroxyanthranic acid inhibits growth of oral squamous carcinoma cells through growth arrest and DNA damage inducible alpha |
| title_fullStr | 3-Hydroxyanthranic acid inhibits growth of oral squamous carcinoma cells through growth arrest and DNA damage inducible alpha |
| title_full_unstemmed | 3-Hydroxyanthranic acid inhibits growth of oral squamous carcinoma cells through growth arrest and DNA damage inducible alpha |
| title_short | 3-Hydroxyanthranic acid inhibits growth of oral squamous carcinoma cells through growth arrest and DNA damage inducible alpha |
| title_sort | 3 hydroxyanthranic acid inhibits growth of oral squamous carcinoma cells through growth arrest and dna damage inducible alpha |
| topic | 3-hydroxyanthranilc acid Oral squamous cell carcinoma Growth arrest and DNA damage inducible alpha tumor proliferation |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000099 |
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