Arecoline N‐oxide regulates oral squamous cell carcinoma development through NOTCH1 and FAT1 expressions

Kuo, Tzer‐Min; Nithiyanantham, Srinivasan; Lee, Chi‐Pin; Hsu, Hui‐Ting; Luo, Shun‐Yuan; Lin, Yun-Hua; Yeh, Kun‐Tu; Ko, Ying‐Chin

doi:10.1002/jcp.28084

Cited by 20 publications

(28 citation statements)

References 57 publications

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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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“…We performed a pancancer analysis of FAT1 mutations. As shown in Figure 3B , FAT1 had the highest mutation frequency in head and neck squamous cell carcinoma, suggesting that FAT1 mutation might play an important role in the occurrence and development of OSCC ( Nishikawa et al, 2011 ; Hayes et al, 2016 ; Hsu et al, 2019 ; Kuo et al, 2019 ). We analyzed the effect of FAT1 mutation on the survival of patients of EUR and AFR.…”

Section: Resultsmentioning

confidence: 95%

Comprehensive Analysis of the Effects of Genetic Ancestry and Genetic Characteristics on the Clinical Evolution of Oral Squamous Cell Carcinoma

Guo

Li²,

Zeng

et al. 2021

Front. Cell Dev. Biol.

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Oral squamous cell carcinoma (OSCC), a kind of malignant cancer, is associated with increasing morbidity and mortality. Patients with different genetic ancestries may respond differently to clinical treatment. The limited understanding of the influence of genetic ancestry and genetic characteristics on OSCC impedes the development of precision medicine. To provide a reference for clinical treatment, this study comprehensively analyzed multigenomic differences in OSCC patients with different genetic ancestries and their impact on prognosis. An analysis of data from OSCC patients with different genetic ancestries in The Cancer Genome Atlas (TCGA) showed that the overall survival (OS) of African (AFR) patients was lower than that of primarily European (EUR) patients, and differences were also observed in the tumor–stroma ratio (TSR) and tumor-infiltrating lymphocytes (TILs), which are associated with prognosis. FAT1 is a key mutant gene in OSCC, and it has inconsistent effects on clinical evolution for patients with diverse genetic characteristics. PIKfyve and CAPN9 showed a significant difference in mutation frequency between EUR and AFR; PIKfyve was related to Ki-67 expression, suggesting that it could promote tumor proliferation, and CAPN9 was related to the expression of Bcl-2, promoting tumor cell apoptosis. A variant methylation locus, cg20469139, was correlated with the levels of PD-L1 and Caspase-7 and modulated tumor cell apoptosis. A novel ceRNA model was constructed based on genetic ancestries, and it could accurately evaluate patient prognosis. More importantly, although T cell dysfunction scores could determine the potential of tumor immune escape, the efficacy was obviously affected by patients’ genetic ancestries. To provide patients with more precise, personalized therapy and to further improve their quality of life and 5-year survival rate, the influence of genetic ancestry should be fully considered when selecting treatments.

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“…At present, there are few studies on arecoline N -oxide. They mainly focus on oral fibrosis [ 26 ] and oral squamous cell carcinoma [ 20 , 27 ]. The former is regulated by Caspase-8, while the latter is regulated by Notch1 and Fat1.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress and Endoplasmic Reticulum Stress Contributes to Arecoline and Its Secondary Metabolites-Induced Dyskinesia in Zebrafish Embryos

Yan

Zhang

et al. 2023

IJMS

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Areca nut has been listed as one of the most addictive substances, along with tobacco, alcohol and caffeine. Areca nut contains seven psychoactive alkaloids; however, the effects of these alkaloids on embryonic development and motor behavior are rarely addressed in zebrafish embryo-larvae. Herein, we investigated the effects of exposure to three alkaloids (arecoline and secondary metabolites—arecaidine and arecoline N-oxide) on the developmental parameters, locomotive behavior, oxidative stress and transcriptome of zebrafish embryos. Zebrafish embryos exposed to different concentrations (0, 0.1, 1, 10, 100 and 1000 μM) of arecoline, arecaidine and arecoline N-oxide showed no changes in mortality and hatchability rates, but the malformation rate of zebrafish larvae was significantly increased in a dose-dependent manner and accompanied by changes in body length. Moreover, the swimming activity of zebrafish larvae decreased, which may be due to the increase in reactive oxygen species and the imbalance between oxidation and antioxidation. Meanwhile, transcriptome analysis showed that endoplasmic reticulum stress and the apoptosis p53 signaling pathway were significantly enriched after exposure to arecoline and arecoline N-oxide. However, arecaidine exposure focuses on protein synthesis and transport. These findings provide an important reference for risk assessment and early warning of areca nut alkaloid exposure.

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Arecoline N‐oxide regulates oral squamous cell carcinoma development through NOTCH1 and FAT1 expressions

Cited by 20 publications

References 57 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

Comprehensive Analysis of the Effects of Genetic Ancestry and Genetic Characteristics on the Clinical Evolution of Oral Squamous Cell Carcinoma

Oxidative Stress and Endoplasmic Reticulum Stress Contributes to Arecoline and Its Secondary Metabolites-Induced Dyskinesia in Zebrafish Embryos

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