Arecoline, a major alkaloid of areca nut, inhibits p53, represses DNA repair, and triggers DNA damage response in human epithelial cells

Tsai, Yi‐Shan; Lee, Ka–Wo; Huang, Jau‐Ling; Liu, Yu-Sen; Juo, Suh‐Hang Hank; Kuo, Wen‐Rei; Chang, Jan‐Gowth; Lin, Chang-Sheng; Jong, Yuh‐Jyh

doi:10.1016/j.tox.2008.05.007

Cited by 115 publications

(119 citation statements)

References 40 publications

(62 reference statements)

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“…43 Recent studies also indicated that arecoline (the major alkaloid of areca nut) might mediate p53 inhibition to influence betel-quid-associated tumorigenesis. 44 Although epidemiological studies have identified betel-quid chewing as a risk factor for ESCC development, among smokers, this investigation further discovered that starting chewing at a younger age is involved in an earlier onset of this neoplasm.…”

Section: Discussionmentioning

confidence: 86%

Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis

Lee¹,

Wu²,

Wu³

et al. 2009

Intl Journal of Cancer

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Genetic variants in alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genes modulate acetaldehyde removal upon alcohol ingestion. Although these genetic vulnerabilities have been linked to higher esophageal squamous cell carcinoma (ESCC) risks, it is unclear whether they also determine the time of malignancy presentation. The purpose of this investigation was to unravel genotoxic effects of the two alcohol-metabolizing genes with regard to alcohol and tobacco consumption on the age at ESCC diagnosis and tumor dissemination. ADH1B/ALDH2 genotyping was performed on lymphocyte DNA specimens taken from 406 consecutively registered incident patients with pathology-proven ESCC. To fully utilize individual genetic and survival information, survival analyses and gene-longevity applied approaches were introduced. Among heavy drinkers, the ADH1B Arg/Arg (55 years) and ALDH2 Glu/Lys genotypes (54 years) were found to confer a 15 and 16 years earlier carcinoma diagnosed age than His/His and Glu/Glu nondrinkers (both 70 years), respectively. For drinkers, 1-year age advancement was, separately, associated with a 0.977 and 0.953-fold stepwise reduced likelihood of being ADH1B Arg homozygote and ALDH2 Lys variant. Noticeably elevated hazard-ratio (HR) for drinkers of ADH1B slow-form genotype and ALDH2 inactive-form allele were identified in smokers (HR 5 2.3-2.6), but no in nonsmokers. In smokers, appreciably higher cumulative cancer onset risks were correspondingly recognized from the age of 45 and 49 upward among any 1 Lys allele and Arg/Arg 1 Glu/Glu combined-ADH1B/ALDH2-genotype drinkers than nondrinkers. In conclusion, consumption of tobacco and alcohol, coupled with genetic susceptibilities associated with acetaldehyde elimination, as modulated by ADH1B and ALDH2 genotypes, determines a substantial magnitude of tumorigenetic effect on earlier age ESCC diagnosis. ' 2009 UICC Key words: age factor; alcohol drinking; alcohol dehydrogenase; aldehyde dehydrogenase; areca; esophageal neoplasms; smoking Carcinoma stemming from the esophagus ranks as the eighth most common cancer in the world and is one of the deadliest and, yet, most neglected forms of cancer.1 Given the insidious nature of this neoplasm, it has been found that more than 50% of the eventual patients already have unresectable and/or metastatic conditions at the time of tumor presentation.2 Although recent advances in the diagnosis, staging and treatment of esophageal cancer have brought about noteworthy improvement toward some manner of survival, 75% of the patients still die within 1 year of diagnosis, and currently just 5-14% of such patients survive at least 5 years.2,3 Due, in part, to the high case fatality rate, younger esophageal carcinoma onset has been linked to a shorter life expectancy. This leads to a number of challenging health-related issues for the respective family, as well as to substantial work productivity losses for the country.Alcohol intake is a well-recognized determinant for squamous cell carcinoma (SCC) of the esopha...

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Section: Discussionmentioning

confidence: 86%

Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis

Lee¹,

Wu²,

Wu³

et al. 2009

Intl Journal of Cancer

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“…In this regard, we have explored the possible effect of arecoline, a major alkaloid in betel nut, on DNA repair activity using HCR. We found that arecoline could inhibit the repair of UV-induced DNA damages, at least partly, through inactivating p53's expression and transactivation activity (Tsai et al, 2008). Besides, we also showed that arecoline could affect mitotic spindles and deregulated mitotic checkpoint, another key guardian of genome integrity (Wang et al, 2010).…”

Section: Some Hnscc Risk Factors Are Able To Inhibit Dna Repairmentioning

confidence: 75%

Application of Host Cell Reactivation in Evaluating the Effects of Anticancer Drugs and Environmental Toxicants on Cellular DNA Repair Activity in Head and Neck Cancer

Tsai¹,

Huang²,

Lin³

2011

Selected Topics in DNA Repair

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“…It is also mutagenic in both bacteria and mammalian cells (Chang et al, 2001). Arecoline was found to inhibit P53, repress DNA repair, and trigger DNA damage response in human epithelial cells via an in-vitro study (Tsai et al, 2008). Chewing betel quid induces local irritation and trauma in the oral mucosa, leading to chronic inflammation, oxidative stress, and cytokine production, and the traumatic wound offers easier access to the system for carcinogens contained in betel quid (Wen et al, 2010).…”

Section: A Literature Analysis Of the Risk Factors For Oral Cancer 69mentioning

confidence: 99%

A Literature Analysis of the Risk Factors for Oral Cancer

Liu¹

2012

Oral Cancer

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Arecoline, a major alkaloid of areca nut, inhibits p53, represses DNA repair, and triggers DNA damage response in human epithelial cells

Cited by 115 publications

References 40 publications

Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis

Genetic modulation of ADH1B and ALDH2 polymorphisms with regard to alcohol and tobacco consumption for younger aged esophageal squamous cell carcinoma diagnosis

Application of Host Cell Reactivation in Evaluating the Effects of Anticancer Drugs and Environmental Toxicants on Cellular DNA Repair Activity in Head and Neck Cancer

A Literature Analysis of the Risk Factors for Oral Cancer

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