Signaling alterations in oral keratinocytes in response to shisha and crude tobacco extract

Abstract

Background: Tobacco consumption in smoking and non-smoking forms has been consequential in the rise of oral cancer cases. Among different forms, epidemiological studies from Middle Eastern countries and rural parts of northern India have reported increasing association of oral cancer with waterpipe (hookah) smoking. However, molecular mechanisms and role played by waterpipe smoking in the onset of oral carcinogenesis remains unexplored. Methods: In this study, immortalized normal human oral keratinocytes were chronically treated with extracts of two varieties of waterpipe tobacco-crude tobacco and processed shisha. Phenotypic changes and molecular aberrations were examined using cell culture-based assays and mass spectrometry-based quantitative proteomic analysis, respectively. Bioinformatics analysis was utilized to analyze proteomics data and identify dysregulated pathways. Results: Our data indicate that chronic treatment with waterpipe tobacco extracts increased proliferation, invasion, migration, and significant dysregulation of protein expression in oral keratinocytes. Altered expression of proteins involved in interferon signaling pathway were observed with both varieties of tobacco. Overexpression of cholesterol metabolism and vesicle-mediated transport proteins were identified exclusively in cells treated with crude tobacco extract. Bioinformatics analyses revealed different oncogenic response in oral cells based on the type of waterpipe tobacco used.Conclusions: This study may serve as a useful resource in understanding the early onset of oral cancer attributed to waterpipe smoking.

Cytotoxic and Genotoxic Effects of Waterpipe on Oral Health Status

“…Two exclusive microbiological studies were removed 27,28 , same to animal studies 29,30 . One study was not found 31 . Manual search has retrieved no additional paper.…”

“…Three studies were in vitro 4,32,33 , and biological samples were obtained from patients in 17 studies 8,31,[33][34][35][36][37][39][40][41][42][43][44][45][46][47][48] . In addition, the levels of pro-inflammatory cytokines, the receptor activator of nuclear factor-κB (RANKL), and osteoprotegerin were evaluated [34][35][36] .…”

“… 27 – 30 However, one study was found but could not be retrieved properly. 31 Furthermore, manual search retrieved no additional papers [ Figure 1 ].…”