Abstract
Smokeless tobacco usage is a growing public health problem worldwide. The molecular mechanism(s) underlying smokeless tobacco associated tissue damage remain largely unidentified. In the present study we have tried to explore the effects of aqueous extract of smokeless tobacco (STE) on tubulin-microtubule, the major cytoskeleton protein that maintains cells morphology and participates in cell division. Exposure to STE resulted in dose-dependent cytotoxicity in a variety of mammalian transformed cell lines such as human lung epithelial cells A549, human liver epithelial cells HepG2, and mouse squamous epithelial cells HCC7, as well as non-tumorogenic human peripheral blood mononuclear cells PBMC. Cellular morphology of STE-treated cells was altered and the associated disruption of microtubule network indicates that STE targets tubulin-microtubule system in both cell lines. Furthermore it was also observed that STE-treatment resulted in the selective degradation of cellular tubulin, whereas actin remains unaltered. In vitro, polymerization of purified tubulin was inhibited by STE with the IC50 value∼150 µg/ml and this is associated with the loss of reactive cysteine residues of tubulin. Application of thiol-based antioxidant N-acetyl cysteine (NAC) significantly abrogates STE-mediated microtubule damage and associated cytotoxicity in both A549 and HepG2 cells. These results suggest that microtubule damage is one of the key mechanisms of STE-induced cytotoxity in mammalian cells.
Highlights
Consumption of smokeless tobacco (ST) as ‘‘spit tobacco’’ or ‘‘chewing tobacco’’ has become a world wide concern for human health due to its increasing adverse effects
These results indicated that exposure to Smokeless Tobacco Extract (STE) a triggers cell death and apoptosis in the cultured mammalian cells
Long-term exposure to ST leads to the formation of oral mucosal lesions and tissue injury [1] but the extent of damage was found to be systemic and contributory to the development of cardiovascular disorders [5], and inflammatory responses in lung and hepatic tissues [31]
Summary
Consumption of smokeless tobacco (ST) as ‘‘spit tobacco’’ or ‘‘chewing tobacco’’ has become a world wide concern for human health due to its increasing adverse effects. Compared to the western world, usage of ST was reported to be more prevalent in South Asian countries [1], recent studies had revealed the world wide usage of ST-related products [2,3]. The placement of ST in mouth, either snuff or chewing tobacco, is known to induce wrinkled changes in the oral mucosa, associated with oral injury and inflammation and may lead to Snuff dipper’s lesion, referred to as leukoplakia. It is characterized by an increased prevalence of gingival recession with associated attachment loss, cervical abrasion, and damage of the oral tissues [1]. Compared to the non users, increased incidence of cardiovascular, renal, and respiratory diseases have been observed in ST-users, as revealed by epidemic studies [6]
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