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Differential effects of areca nut, tobacco, and lime on oral squamous cell carcinoma progression Authors

ABSTRACT: Consumption of tobacco and its associated products has been linked with a high incidence of oral cancer in the Indian subcontinent. The present study aims to assess the differential effect of areca nut, tobacco, and slaked lime on the pathogenesis and progression of oral cancer. Extracts of areca nut (ANE), tobacco leaf (TLE), and lime water (LWE) were prepared and characterized. Oral keratinocyte cells (BICR10) were treated with the prepared extracts alone and in combinations. Cell apoptosis, necrosis, nuclear aberrations, and transcript expression profiles were assessed to study the cancer pathogenesis. An increase in apoptosis and necrosis was observed in the cells treated with ANE and ANE+LWE, while a decrease in apoptosis was observed in cells treated with TLE. We also found a variation in the size of nuclei and an increase in the number of multinuclei in the cells treated with TLE and TLE+LWE. Out of twenty-four head and neck cancer-related genes, we found significant upregulation in seven genes in ANE, six in ANE+LWE, thirteen in TLE, twenty in LWE, and fourteen in TLE+LWE treated cells. On pathway enrichment analysis, there were alterations in the 'pathways in cancer,' 'focal adhesion,' and 'amoebiasis.' In conclusion, although areca nut has been regarded as a carcinogen, its carcinogenic potential is lesser than tobacco and lime. Moreover, adjunctive use of tobacco and lime along with areca nut may be an essential factor in the onset and progression of oral cancer.

ORGANISM(S): Homo sapiens (human)

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PROVIDER: S-BSST1495 | biostudies-other |

REPOSITORIES: biostudies-other

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Areca nut extract demonstrated apoptosis-inducing mechanism by increased caspase-3 activities on oral squamous cell carcinoma.

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| S-EPMC6668048 | biostudies-literature

Betel Nut (areca) and Smokeless Tobacco Use in Myanmar.

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Ultrasonographic evaluation of oral submucous fibrosis in habitual areca nut chewers.

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Salivary Areca and tobacco alkaloids for bioverification in the Betel Nut Intervention Trial.

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Long non-coding RNA expression profiles and related regulatory networks in areca nut chewing-induced tongue squamous cell carcinoma.

Project description:Areca nut chewing is an important risk factor for developing tongue squamous cell carcinoma (TSCC), although the underlying molecular mechanism is unknown. To determine the potential molecular mechanisms of areca nut chewing-induced TSCC, the present study performed whole-genome detection with five pairs of TSCC and adjacent normal tissues, via mRNA- and long non-coding (lnc)RNA-gene chip analysis. A total of 3,860 differentially expressed genes were identified, including 2,193 lncRNAs and 1,667 mRNAs. Gene set-enrichment analysis revealed that the differentially expressed mRNAs were enriched in chromosome 22q13, 8p21 and 3p21 regions, and were regulated by nuclear factor kappa B (NF-?B) and interferon regulatory factors (IRFs). The results of ingenuity pathway analysis revealed that these mRNAs were significantly enriched for inflammatory immune-related signaling pathways. A co-expression network of mRNAs and lncRNAs was constructed by performing weighted gene co-expression network analysis. The present study focused on NF-?B-, IRF- and Th cell-signaling pathway-related lncRNAs and the corresponding mRNA-lncRNA regulatory networks. To the best of our knowledge, the present study was the first to investigate differential mRNA- and lncRNA-expression profiles in TSCCs induced by areca nut chewing. Inflammation-related mRNA-lncRNA regulatory networks driven by IRFs and NF-?B were identified, as well as the Th cell-related signaling pathways that play important carcinogenic roles in areca nut chewing-induced TSCC. These differentially expressed mRNAs and lncRNAs, and their regulatory networks provide insight for further analysis on the molecular mechanism of areca nut chewing-induced TSCC, candidate molecular markers and targets for further clinical intervention.

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Project description: Not available

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Project description: Not available

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Methylation-associated gene silencing of RARB in areca carcinogens induced mouse oral squamous cell carcinoma.

Project description:Regarding oral squamous cell carcinoma (OSCC) development, chewing areca is known to be a strong risk factor in many Asian cultures. Therefore, we established an OSCC induced mouse model by 4-nitroquinoline-1-oxide (4-NQO), or arecoline, or both treatments, respectively. These are the main two components of the areca nut that could increase the occurrence of OSCC. We examined the effects with the noncommercial MCGI (mouse CpG islands) microarray for genome-wide screening the DNA methylation aberrant in induced OSCC mice. The microarray results showed 34 hypermethylated genes in 4-NQO plus arecoline induced OSCC mice tongue tissues. The examinations also used methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing to realize the methylation pattern in collected mouse tongue tissues and human OSCC cell lines of different grades, respectively. These results showed that retinoic acid receptor ? (RARB) was indicated in hypermethylation at the promoter region and the loss of expression during cancer development. According to the results of real-time PCR, it was shown that de novo DNA methyltransferases were involved in gene epigenetic alternations of OSCC. Collectively, our results showed that RARB hypermethylation was involved in the areca-associated oral carcinogenesis.

| S-EPMC4150525 | biostudies-literature

LncRNA expression profiles in areca nut chewing induced Tongue Squamous Cell Carcinoma (TSCC) and matched paracancerous tissues

Project description:Chewing betel nut is an important risk factor for the carcinogenesis of tongue squamous cell carcinoma (TSCC), but the mechanism is still unknown.To screen the lncRNAs associated with betel nut chewing-induced TSCC and identify potential biomarkers for the TSCC, we collected 5 pairs of TSCC and paracancerous tissues and monitored the resultant lncRNA and mRNA expression profiles using an lncRNA microarray. All 5 patients have a history of areca nut chewing.

2020-10-27 | GSE139869 | GEO

Areca nut consumption with and without tobacco among the adult population: a nationally representative study from India.

Project description:ObjectiveAreca nut is one of the most widely consumed substances globally, after nicotine, ethanol and caffeine and classified as carcinogenic to humans. This study examines the disparity and determinants of areca nut consumption with and without tobacco in India.DesignNationally representative cross-sectional study.ParticipantsWe used the nationally representative Global Adult Tobacco Survey 2016-2017. The analytical sample size was 74 037 individual's aged 15 years and above with a response rate of 92.9%.MeasuresCurrent consumption of areca nut without tobacco and with tobacco.MethodWe examined determinants of areca nut consumption (without tobacco and with tobacco) using multinomial logistic regression, accounting for the survey design.ResultsAbout 23.9% (95% CI 23.1 to 24.8) of the adult population consume areca nut, that is, approximately 223.79 million people in India; majority of users (14.2%-95% CI 13.5 to 14.9) consumed areca nut with tobacco. When compared with women, men were more likely to consume areca nut (with tobacco relative risk (RR)=2.02; 95% CI 1.85 to 2.21 and without tobacco RR=1.13; 95% CI 1.07 to 1.20). Age, marital status, education, occupation, caste, religion and region were significantly associated with areca nut consumption. However, the direction and magnitude of association differ with respect to the areca nut consumption with and without tobacco.ConclusionThe ongoing tobacco control efforts would not address the majority of areca nut users until greater attention to areca nut consumption with and without tobacco is reflected in health policies in India.

| S-EPMC8208015 | biostudies-literature

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