Co-treating with arecoline and 4-nitroquinoline 1-oxide to establish a mouse model mimicking oral tumorigenesis

Chang, Nai Wen; Pei, Renjun; Tseng, Hsien Chang; Yeh, Kun Tu; Chan, Hsu Chin; Lee, Miau Rong; Lin, Chi‐Tsai; Hsieh, Wen Tsong; Kao, Ming‐Ching; Tsai, Ming Hsui; Lin, Chin Fen

doi:10.1016/j.cbi.2009.10.005

Cited by 57 publications

(60 citation statements)

References 21 publications

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“…Many previous researches have demonstrated that arecoline is the main etiological factor for the development of OSCC (Chang et al 2010;Cheng et al 2013). In 1999, a study was undertaken to determine the differences in genotoxic effects of arecoline by two different administration routes, including oral administration (p.o.)…”

Section: Toxicologymentioning

confidence: 99%

The pharmacology, toxicology and potential applications of arecoline: a review

Liu

Peng

et al. 2016

Pharmaceutical Biology

113

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Context: Arecoline is an effective constituent of Areca catechu L. (Arecaceae) with various pharmacological effects. However, investigations also revealed that long use of arecoline could arouse some oral diseases. Objective: The present review gathers the fragmented information available in the literature (before 1 October 2015) regarding pharmacology and toxicology of arecoline. We also discussed the potential developments and applications of arecoline in the future. Methods: All the available information regarding the arecoline is compiled from scientific databases, including Science Direct, PubMed, Web of Science, Scopus, etc. Results: Previous research demonstrated that arecoline is one of the major effective constituents in A. catechu. Additionally, arecoline has a wide spectrum of pharmacological activities including effects on nervous, cardiovascular, digestive and endocrine systems and anti-parasitic effects. What's more, arecoline is reported to be the primary toxic constituent of A. catechu, and the main toxic effects include oral submucous fibrosis (OSF), oral squamous cell carcinoma (OSCC) and genotoxicity. Conclusion: Arecoline has great potential to be a therapeutic drug for various ailments. However, further investigations are needed in the future to reduce or eliminate its toxicities before developing into new drug. ARTICLE HISTORY

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Section: Toxicologymentioning

confidence: 99%

The pharmacology, toxicology and potential applications of arecoline: a review

Liu

Peng

et al. 2016

Pharmaceutical Biology

113

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“…26 In one study focused on the induction of oral lesions or tumor formation, cotreatment with arecoline and 4-NQO of tobacco-related carcinogen induced tongue tumors in mice; however, arecoline alone did not induce any oral pathological lesions. 27 In addition, 3-(methymitrosamino)propionitriIe (MNPN) and N-(nitrosomethylamino)propionitrile (NMAP), lime-enhancing synthesized derivatives from the areca nut in saliva, showed lower effects on tumor induction in the oral cavity of rats. 28 Although a strong association between oral precancer or cancer and betel chewing has been demonstrated, 3 the results from multiple animal studies have not proven that there is a link.…”

Section: Journal Of Agricultural and Food Chemistrymentioning

confidence: 99%

Fibrotic Effects of ArecolineN-Oxide in Oral Potentially Malignant Disorders

Kuo

Luo

Chiang

et al. 2015

J. Agric. Food Chem.

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The metabolites of environmental chemicals play key roles in carcinogenesis. Areca nut is strongly associated with the development of oral potentially malignant disorders (OPMD) or cancer. The main alkaloid in the areca nut is arecoline, which is highly cytotoxic and genotoxic. Arecoline N-oxide, a metabolite of areca nut alkaloids, which has been identified in animal urine, has been shown to induce mutagenicity in bacteria. In this study, it was found that its protein adduct could be detected in oral keratinocytes treated with areca nut extract. Increased collagen expression and severity of squamous hyperplasia were observed in arecoline N-oxide treated mice. In cultured oral fibroblasts, arecoline N-oxide showed stronger effects on the increase of fibrotic related genes including TGF-beta1, S100A4, MMP-9, IL-6, and fibronectin and a decrease of E-cadherin as compared with arecoline. Finally, arecoline N-oxide stimulation effectively increased the DNA damage marker, gamma-H2A.X, both in vitro and in vivo. Taken together, these results indicate that arecoline N-oxide shows a high potential for the induction of OPMD.

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“…Currently it has started to be used simultaneously 4-NQO (200 µg/ mL) more and arecoline (500 µg/mL), in order to increase the incidence of malignant lesions (Chang et al, 2010). The 4NQO model is still the most used, however, transgenic models are very recent and very promising, considering that the genetics of animals is known, these models seek to standardize the model of oral carcinogenesis, an example of them, the K14-CreERtam/LSL-K-rasG12D/ +/p53flox/flox two-hit animal model system (Raimondi et al, 2009) that may represent a suitable platform for exploring the underlying molecular mechanism and genetic and epigenetic event determining the susceptibility to malignant progression of tumoral lesions arising from the distinct stratified epithelia of the oral cavity.…”

Section: Discussionmentioning

confidence: 99%