How Each Component of Betel Quid Is Involved in Oral Carcinogenesis: Mutual Interactions and Synergistic Effects with Other Carcinogens—a Review Article

Islam, Saidul; Muthumala, Malsantha; Matsuoka, Hirofumi; Uehara, Osamu; Kuramitsu, Yasuhiro; Chiba, Itsuo; Abiko, Yoshihiro

doi:10.1007/s11912-019-0800-8

Cited by 38 publications

(35 citation statements)

References 88 publications

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“…The oral microbiome population might promote carcinogenesis by increasing oxidative stress in the oral cavity of people with adverse lifestyle habits such as smoking, alcohol drinking and betel chewing [22]. But it is still unclear what role the oral bacteria play exactly in the development of oral cancer.…”

Section: Introductionmentioning

confidence: 99%

Clostridium perfringens enterotoxin induces claudin-4 to activate YAP in oral squamous cell carcinomas

et al. 2020

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Claudin (CLDN)-4 expression has been associated with malignancy in various cancers. When CLDN4 expression was examined in oral squamous cell carcinoma (OSCC), 22 out of 57 (39%) cases showed immunoreactivity in the nucleus. Nuclear CLDN4-positive cases showed a stronger correlation with cancer progression than the negative cases. Intratumoral anaerobic bacterial DNA examination revealed nuclear CLDN4 expression in 81% of Clostridium perfringens-positive cases. Treatment of human oral squamous cell carcinoma cell lines HSC3 and HSC4 with Clostridium perfringens enterotoxin (CPE), induced CLDN4 nuclear translocation to enhance epithelial-mesenchymal transition (EMT), stemness, cell proliferation and invasive ability. In addition, CPE treatment suppressed phosphorylation of yes-associated protein-1 (YAP1) and promoted YAP1 nuclear translocation, resulting in increased expression of YAP1 target genes; cyclin D1 and connective tissue growth factor. Moreover, it was revealed that the complex of YAP1, CLDN4 and zona occludens-2 (ZO-2) was formed by CPE treatment, further suppressing YAP1 phosphorylation by LATS1 and activating it. Thus YAP activation in OSCC was regarded important in promoting malignant phenotypes. Our research suggested that the control of oral anaerobic bacteria may suppress YAP activation and in turn tumor progression.

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Section: Introductionmentioning

confidence: 99%

Clostridium perfringens enterotoxin induces claudin-4 to activate YAP in oral squamous cell carcinomas

et al. 2020

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“…MeCP2 has been shown to interact with DNA methyltransferase 1 (DNMT1) and recruits the latter to induce SIRT1 promoter methylation [26]. Arecoline was previously documented to promote oral submucosal fibrosis and the progression to oral cancer through pathways involved in transforming growth factor-beta (TGF-β) production [2,27]. TGF-β is likely to silence SIRT1 epigenetically by inducing the MeCP2 expression, although other possible mechanisms cannot be ruled out [26].…”

Section: Discussionmentioning

confidence: 99%

“…The habit of betel quid (BQ) chewing is considered to be a significant risk factor for oral cancer and oral mucosal diseases in South and Southeast Asian countries [1][2][3]. BQ may be considered as any quid comprised of betel leaf and a combination of areca nut and slaked lime, with or without tobacco.…”

Section: Introductionmentioning

confidence: 99%

“…BQ may be considered as any quid comprised of betel leaf and a combination of areca nut and slaked lime, with or without tobacco. Each component in BQ may individually, synergistically, and coordinately participate in carcinogenesis [2]. However, the underlying molecular mechanisms for the development of oral cancer remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…However, the physiological relevance of SIRT1 in BQ-related oral cancer remains unexplored. BQ-related oral cancer is often preceded by the development of precancerous lesions, characterized by the disruption of epithelial integrity and, consequently, the transformation to invasive cancer [2]. Intriguingly, SIRT1 has been identified as playing a role in the maintenance of epithelial integrity and contributing to the prevention of both the invasion and metastasis potential of the oral epithelium [17].…”

Section: Introductionmentioning

confidence: 99%

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DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing—a possible predictive biomarker for malignant transformation

et al. 2020

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Background: DNA hypermethylation of tumor suppressor genes is observed in precancerous lesions and oral cancer of individuals with the habits of betel quid (BQ) chewing. SIRT1 has been identified as playing a role in the maintenance of epithelial integrity, and its alteration is often related to carcinogenesis. However, the methylation and transcription status of SIRT1 in patients with BQ chewing-related oral cancer has not been investigated. We examined the methylation status of SIRT1 in paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC) obtained from BQ chewing and non-chewing patients and in tissue samples from healthy control subjects. In addition, we examined whether the hypermethylation of SIRT1 followed by its transcriptional downregulation in the human gingival epithelial cells could be caused by arecoline, a major component of BQ. Furthermore, we investigated the methylation status of SIRT1 in smear samples of macroscopically healthy buccal mucosa from subjects with a habit of BQ chewing. Results: SIRT1 was significantly hypermethylated in tissue samples of OSCC from BQ chewers and non-chewers than in oral mucosa from healthy control subjects. Results also showed that the hypermethylation level of SIRT1 was significantly higher in OSCC of patients with BQ chewing habits than in those of non-chewing habits (p < 0.05). Our in vitro model showed that hypermethylation is followed by downregulation of the transcriptional level of SIRT1 (p < 0.05). The methylation levels of SIRT1 in the smear samples obtained from BQ chewing individuals were significantly higher than those in the samples obtained from individuals that did not chew BQ. The duration of BQ chewing habits was correlated positively to the frequency of SIRT1 hypermethylation (p < 0.05). Conclusions: Our results suggest that DNA hypermethylation of SIRT1 is involved in the occurrence of oral cancer in BQ chewing patients and that hypermethylation in the oral mucosa of BQ chewers could be a predictive marker for the occurrence of malignant transformation. This is the first report that showed DNA hypermethylation in clinically healthy oral epithelium of BQ chewers. Our study shows evidence that DNA hypermethylation may be an early event of oral carcinogenesis prior to observable clinical changes.

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Oral Microbiome and Oral Cancer

Perera

Tilakaratne

2023

Immunology for Dentistry

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How Each Component of Betel Quid Is Involved in Oral Carcinogenesis: Mutual Interactions and Synergistic Effects with Other Carcinogens—a Review Article

Cited by 38 publications

References 88 publications

Clostridium perfringens enterotoxin induces claudin-4 to activate YAP in oral squamous cell carcinomas

Clostridium perfringens enterotoxin induces claudin-4 to activate YAP in oral squamous cell carcinomas

DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing—a possible predictive biomarker for malignant transformation

Oral Microbiome and Oral Cancer

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