Cytotoxic Effects Produced by Arecoline Correlated to Epigenetic Regulation in Human K-562 Cells

Lin, Pei‐Chin; Chang, Wen‐Dien; Chen, Yung-Hsiu; Lee, Chien-Chih; Lin, Yi‐Hsiung; Chang, Jan-Gowth

doi:10.1080/15287394.2011.539123

Cited by 18 publications

(20 citation statements)

References 27 publications

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“…They observed that arecoline produced changes in the expression of several genes catalyzing histone methylation (Mll, Setdb1, and Suv39h2), acetylation (Atf2), and demethylation (JMJD6). Since H3K9 methylation is involved in maintaining the stability of heterochromatin structures and inactivating euchromatic gene expressions, this study indicates that arecoline-induced epigenetic changes play a role in the mechanisms underlying chemical-mediated cytotoxicity and genotoxicity [39].…”

Section: Resultsmentioning

confidence: 78%

Association of Betel Nut with Carcinogenesis: Revisit with a Clinical Perspective

et al. 2012

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Betel nut (BN), betel quid (BQ) and products derived from them are widely used as a socially endorsed masticatory product. The addictive nature of BN/BQ has resulted in its widespread usage making it the fourth most abused substance by humans. Progressively, several additives, including chewing tobacco, got added to simple BN preparations. This addictive practice has been shown to have strong etiological correlation with human susceptibility to cancer, particularly oral and oropharyngeal cancers.The PUBMED database was searched to retrieve all relevant published studies in English on BN and BQ, and its association with oral and oropharyngeal cancers. Only complete studies directly dealing with BN/BQ induced carcinogenesis using statistically valid and acceptable sample size were analyzed. Additional relevant information available from other sources was also considered.This systematic review attempts to put in perspective the consequences of this widespread habit of BN/BQ mastication, practiced by approximately 10% of the world population, on oral cancer with a clinical perspective. BN/BQ mastication seems to be significantly associated with susceptibility to oral and oropharyngeal cancers. Addition of tobacco to BN has been found to only marginally increase the cancer risk. Despite the widespread usage of BN/BQ and its strong association with human susceptibility to cancer, no serious strategy seems to exist to control this habit. The review, therefore, also looks at various preventive efforts being made by governments and highlights the multifaceted intervention strategies required to mitigate and/or control the habit of BN/BQ mastication.

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Section: Resultsmentioning

confidence: 78%

Association of Betel Nut with Carcinogenesis: Revisit with a Clinical Perspective

et al. 2012

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“…Clinically, low dose intravenous application of arecoline hydrobromide has been used to treat Alzheimer's disease (Christie et al, 1981; Tariot et al, 1988). Arecoline hydrobromide was reported to induce HA22T/VGH hepatoma cells to undergo anoikis (Cheng et al, 2010) and arecoline causes epigenetic changes in K562 leukemia cells that lead to chemical-mediated cytotoxicity and genotoxicity (Lin et al, 2011). However, arecoline has also been associated with the development of oral premalignant lesions and risk of oral cancer in many areas of Asia, the Pacific region, and in migrant communities in the United Kingdom, United States and South Africa where betel chewing is prevalent (Gupta and Warnakulasuriya, 2002; Sharan et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Tetrameric Acetyl-CoA Acetyltransferase 1 Is Important for Tumor Growth

et al. 2016

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SUMMARY Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) regulates pyruvate dehydrogenase complex (PDC) by acetylating pyruvate dehydrogenase (PDH) and PDH phosphatase. How ACAT1 is “hijacked” to contribute to the Warburg effect in human cancer remains unclear. We found that active, tetrameric ACAT1 is commonly upregulated in cells stimulated by EGF and in diverse human cancer cells, where ACAT1 tetramers but not monomers are phosphorylated and stabilized by enhanced Y407-phosphorylation. Moreover, we identified arecoline hydrobromide (AH) as a covalent ACAT1 inhibitor, which binds to and disrupts only ACAT1 tetramers. The resultant AH-bound ACAT1 monomers cannot reform tetramers. Inhibition of tetrameric ACAT1 by abolishing Y407-phosphorylation or AH treatment results in decreased ACAT1 activity, leading to increased PDC flux and oxidative phosphorylation with attenuated cancer cell proliferation and tumor growth. These findings provide a mechanistic understanding of how oncogenic events signal through distinct acetyltransferases to regulate cancer metabolism, and suggest ACAT1 as an anti-cancer target.

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“…In addition, arecoline impeded DNA repair and mitotic spindle assembly . Recently, arecoline was suggested to regulate the expression of certain genes through epigenetic control …”

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confidence: 99%

Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma

Yang

Chen

et al. 2012

Cancer Science

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Arecoline, the major alkaloid of areca nut, has been shown to cause strong genotoxicity and is considered a potential carcinogen. However, the detailed mechanism for arecoline‐induced carcinogenesis remains obscure. In this study, we noticed that the levels of p21 and p27 increased in two oral squamous cell carcinoma cell lines with high confluence. Furthermore, when treated with arecoline, elevated levels of p21 and p27 could be downregulated through the reactive oxygen species/mTOR complex 1 (ROS/mTORC1) pathway. Although arecoline decreased the activity of mTORC1, the amounts of autophagosome‐like vacuoles or type II LC3 remained unchanged, suggesting that the downregulation of p21 and p27 was independent of autophagy‐mediated protein destruction. Arecoline also caused DNA damage through ROS, indicating that the reduced levels of p21 and p27 might facilitate G 1/S transition of the cell cycle and subsequently lead to error‐prone DNA replication. In conclusion, these data have provided a possible mechanism for arecoline‐induced carcinogenesis in subcytolytic doses in vivo. (Cancer Sci 2012; 103: 1221–1229)

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Cytotoxic Effects Produced by Arecoline Correlated to Epigenetic Regulation in Human K-562 Cells

Cited by 18 publications

References 27 publications

Association of Betel Nut with Carcinogenesis: Revisit with a Clinical Perspective

Association of Betel Nut with Carcinogenesis: Revisit with a Clinical Perspective

Tetrameric Acetyl-CoA Acetyltransferase 1 Is Important for Tumor Growth

Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma

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