Effect of cigarette smoke extract on mitochondrial heme-metabolism: An in vitro model of oral cancer progression

Tobacco smoking is considered as one of the major risk factors for development of oral cancer. In vitro studies indicate that cigarette smoke initiates transformation of epithelial cells toward development of oral cancer through altering mitochondrial metabolic pathways. However the present in vitro models need to be improved to correlate these molecular changes with epithelial transformations. In present study, we investigated the association of mitochondrial metabolic events with oral cancer progression under cigarette smoke extract (CSE). In this regard, an in vitro model of oral keratinocyte cell line (MOE1A) was developed by exposing them with different concentrations of CSE. Alterations in cellular phenomena were confirmed by Fourier-transform infrared spectroscopy (FTIR) study, which indicated changes in important functional groups of CSE-induced oral cells. Enhanced reactive oxygen species (ROS) of exposed cells altered the mitochondrial metabolic activities in terms of increased mitochondrial mass and DNA content. Further, mitochondrial heme-metabolism was investigated and real-time PCR study showed altered expression of important genes like ALAS1, ABCB6, CPOX, FECH, HO-1. Both transcriptomic and proteomic studies showed up- and down-regulation of important biomarkers related to cellular cancer progression. Overall data suggest that CSE alters mitochondrial heme metabolic pathway and initiates cancer progression through modifying cellar biomarkers in oral epithelial cells. Schismatic represents CSE exposure increased cytotoxicity and cell death through ROS generation in oral keratinocyte cells. Increased ROS generation altered oxidative stress and mitochondrial bioenergetics via increasing heme production and expression of heme oxygenase (HO-1) gene. Enhanced ROS developed epithelial to mesenchymal transition (EMT) through disturbing cell-cell junction and imitated metastasis and cell death. [Display omitted] •Cigarette smoke extract (CSE) induced cytotoxicity on oral epithelial cells.•CSE enhanced oxidative stress by increasing ROS.•CSE increased mitochondrial mass and DNA content.•CSE altered mitochondrial heme metabolic pathway under high oxidative stress.•CSE may initiate oral cancer progression through induction of EMT.