Arecoline‐regulated ataxia telangiectasia mutated expression level in oral cancer progression

Tu, Hsi Feng; Chen, Michael Yuanchien; Lai, Joseph Chieh Yui; Chen, Yi Ling; Wong, Yih Wen; Yang, Cheng Chieh; Chen, Hsin Yuan; Hsia, Shih Min; Shih, Yin Hwa; Shieh, Tzong‐Ming

doi:10.1002/hed.25718

Cited by 21 publications

(26 citation statements)

References 40 publications

(51 reference statements)

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“…Arecoline is an alkaloid extracted from betel nut and plays an essential role in the progression of oral cancer (101,102). Chang et al (38) treated C57BL/6JNarl mice with arecoline, 4NQO, or both arecoline and 4NQO for 8 weeks to induce oral carcinogenesis.…”

Section: Nqo Combined With Other Chemical Carcinogens 4nqo and Arecomentioning

confidence: 99%

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Dong

Yang

et al. 2020

Front. Oncol.

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Preclinical animal models of oral squamous cell carcinoma (OSCC) have been extensively studied in recent years. Investigating the pathogenesis and potential therapeutic strategies of OSCC is required to further progress in this field, and a suitable research animal model that reflects the intricacies of cancer biology is crucial. Of the animal models established for the study of cancers, mouse tumor-bearing models are among the most popular and widely deployed for their high fertility, low cost, and molecular and physiological similarity to humans, as well as the ease of rearing experimental mice. Currently, the different methods of establishing OSCC mouse models can be divided into three categories: chemical carcinogen-induced, transplanted and genetically engineered mouse models. Each of these methods has unique advantages and limitations, and the appropriate application of these techniques in OSCC research deserves our attention. Therefore, this review comprehensively investigates and summarizes the tumorigenesis mechanisms, characteristics, establishment methods, and current applications of OSCC mouse models in published papers. The objective of this review is to provide foundations and considerations for choosing suitable model establishment methods to study the relevant pathogenesis, early diagnosis, and clinical treatment of OSCC.

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Section: Nqo Combined With Other Chemical Carcinogens 4nqo and Arecomentioning

confidence: 99%

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Dong

Yang

et al. 2020

Front. Oncol.

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“…The results showed that arecoline was able to inhibit ATM promoter activity in a dose-dependent manner ( Figure 1 E). Tu et al and our unpublished data also showed that arecoline could decrease ATM promoter activity in SAS, OEC-M1 [ 32 ], and KB cells (data not shown). These results indicate that ANE and arecoline suppress the expression of ATM and BRCA1 in hGFs and cancer cells.…”

Section: Resultsmentioning

confidence: 63%

“…Previously, we have reported an association between low ATM expression and poor patient outcome in laryngeal and pharyngeal cancers [ 8 ]. Yu et al also found that low ATM expression was correlated with a worse OS in oral cancer [ 32 ]. The HNC patients both in Yu et al’s and our studies have a habit of chewing betel quid (BQ), which ingredients may suppress the expression of ATM and BRCA1 [ 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

“…Yu et al also found that low ATM expression was correlated with a worse OS in oral cancer [ 32 ]. The HNC patients both in Yu et al’s and our studies have a habit of chewing betel quid (BQ), which ingredients may suppress the expression of ATM and BRCA1 [ 32 , 33 ]. The promoting effect of BQ on the development of HNC has been demonstrated by epidemiological investigations [ 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of ATM and BRCA1 Predicts Poor Outcome in Head and Neck Cancer: Implications for ATM-Targeted Therapy

Wang

Lee

Tsai

et al. 2021

JPM

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ATM and BRCA1 are DNA repair genes that play a central role in homologous recombination repair. Alterations of ATM and BRCA1 gene expression are found in cancers, some of which are correlated with treatment response and patient outcome. However, the role of ATM and BRCA1 gene expression in head and neck cancer (HNC) is not well characterized. Here, we examined the prognostic role of ATM and BRCA1 expression in two HNC cohorts with and without betel quid (BQ) exposure. The results showed that the expression of ATM and BRCA1 was downregulated in BQ-associated HNC, as the BQ ingredient arecoline could suppress the expression of both genes. Low expression of either ATM or BRCA1 was correlated with poor overall survival (OS) and was an independent prognostic factor in multivariate analysis (ATM HR: 1.895, p = 0.041; BRCA1 HR: 2.163, p = 0.040). The combination of ATM and BRCA1 expression states further improved on the prediction of OS (HR: 4.195, p = 0.001, both low vs. both high expression). Transcriptomic analysis showed that inhibition of ATM kinase by KU55933 induced apoptosis signaling and potentiated cisplatin-induced cytotoxicity. These data unveil poor prognosis in the HNC patient subgroup with low expression of ATM and BRCA1 and support the notion of ATM-targeted therapy.

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“…Arecoline is the major compound in betel nut that initiates the OSF process [ 41 , 42 , 43 ]. Low doses of arecoline enhance the cell proliferation rate, while high doses of arecoline induce total reactive oxygen species (ROS), DNA damage, and LOX activity [ 44 ]. The ataxia-telangiectasia mutated activated DNA repair is also inhibited by arecoline [ 45 ].…”

Section: Epidemiology Of Osfmentioning

confidence: 99%

Oral Submucous Fibrosis: A Review on Biomarkers, Pathogenic Mechanisms, and Treatments

Shen

Shih

Fuh

et al. 2020

IJMS

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Oral submucous fibrosis (OSF) is a collagen deposition disorder that affects a patient’s oral function and quality of life. It may also potentially transform into malignancy. This review summarizes the risk factors, pathogenic mechanisms, and treatments of OSF based on clinical and bio-molecular evidence. Betel nut chewing is a major risk factor that causes OSF in Asia. However, no direct evidence of arecoline-induced carcinogenesis has been found in animal models. Despite identification of numerous biomarkers of OSF lesions and conducting trials with different drug combinations, clinicians still adopt conservative treatments that primarily focus on relieving the symptoms of OSF. Treatments focus on reducing inflammation and improving mouth opening to improve a patient’s quality of life. In conclusion, high-quality clinical studies are needed to aid clinicians in developing and applying molecular biomarkers as well as standard treatment guidelines.

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Arecoline‐regulated ataxia telangiectasia mutated expression level in oral cancer progression

Cited by 21 publications

References 40 publications

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Downregulation of ATM and BRCA1 Predicts Poor Outcome in Head and Neck Cancer: Implications for ATM-Targeted Therapy

Oral Submucous Fibrosis: A Review on Biomarkers, Pathogenic Mechanisms, and Treatments

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