Carcinogenic Effects of Areca Nut and Its Metabolites: A Review of the Experimental Evidence

Abstract

Oral cancers (OC) are among the most frequent malignancies encountered in Southeast Asia, primarily due to the prevalent habit of betel quid (BQ) and smokeless tobacco use in this region. Areca nut (AN), the primary ingredient in BQ, contains several alkaloids, including arecoline, arecaidine, guvacoline, and guvacine. These have been associated with both the AN abuse liability and carcinogenicity. Additionally, variations in AN alkaloid levels could lead to differences in the addictiveness and carcinogenic potential across various AN-containing products. Recent studies based on animal models and in vitro experiments show cellular and molecular effects induced by AN. These comprise promoting epithelial-mesenchymal transition, autophagy initiation, tissue hypoxia, genotoxicity, cytotoxicity, and cell death. Further, clinical research endorses these undesired harmful effects in humans. Oral submucosal fibrosis, a potentially malignant disease of the oral cavity, is predominantly reported from the geographical areas of the globe where AN is habitually chewed. OC in chronic AN users presents a more aggressive phenotype, such as resistance to anti-cancer drugs. The available evidence on the carcinogenicity of AN based on the findings reported in the recently published experimental studies is discussed in the present review.

The association of ethnicity and oncologic outcomes for oral cavity squamous cell carcinoma (OSCC)

“…One of the major factors is thought to be the use of betel nut in the SA culture, which is commonly consumed in the form of betel quid. Although the added tobacco plays a significant role in the development of OSCCs, studies have suggested that betel products, which contain arecoline and 3-(methylnitrosamino) propionitrile, may have an independent carcinogenic effect (35) resulting in malignant transformation of oral submucosal fibrosis (OSMF). The potential for malignant transformation resulting in OSCC has been reported to be as high as 7 to 13% (36).…”

“…Univariate Kaplan-Meier analysis revealed that patients of SA ethnicity had worse RFS [HR=2. 35 (1.51-3.65)] than those of non-SA ethnicity (Figure 2A). RFS for SA patients at 3-year follow up was 52%, compared to 76% in the non-SA group (p<0.01).…”

Nanoplatforms: The future of oral cancer treatment

“…6 Oral cancer can be influenced by various factors such as excessive tobacco consumption (both smoked and smokeless forms), betel nut chewing, alcohol, and chronic inflammation. 7,8 Human papillomavirus-related (mostly HPV16) oral and oropharyngeal malignancies have become more common in young people in recent decades. [9][10][11] In the realm of oncology, chemotherapy is the anticancer therapy that is most frequently used.…”

“…Oral cancer incidence rises with age, peaking in persons over 60 and among those under 40 years 6 . Oral cancer can be influenced by various factors such as excessive tobacco consumption (both smoked and smokeless forms), betel nut chewing, alcohol, and chronic inflammation 7,8 . Human papillomavirus‐related (mostly HPV16) oral and oropharyngeal malignancies have become more common in young people in recent decades 9–11 …”

Brief psychotic disorder caused by areca nut use: a case report

“…Furthermore, China stands as the second-largest producer of areca nut globally 3 . Despite its popularity, areca nut is classi ed as carcinogenic to humans and has been linked to a range of detrimental health effects, including carcinogenicity 4 , genetic and epigenetic instability 5 , sub-mucous brosis progression 6 , oral cancer 7 , and liver disease 8 .…”