Nicotine-induced oxidative stress contributes to EMT and stemness during neoplastic transformation through epigenetic modifications in human kidney epithelial cells.

摘要: Nicotine is a component of cigarette smoke and mounting evidence suggests toxicity carcinogenicity tobacco in kidney. Carcinogenicity nicotine itself kidney the underlying molecular mechanisms are not well-understood. Hence, objective this study was to determine carcinogenic effects chronic exposure Hk-2 human epithelial cells. The on expression genes for cellular reprogramming, redox status, growth signaling pathways were also evaluated understand mechanisms. Results revealed that induced neoplastic transformation HK-2 Increased levels intracellular reactive oxygen species (ROS), acquired stem cell-like sphere formation, epithelial-mesenchymal-transition (EMT) changes observed exposed Treatment with antioxidant N-acetyl cysteine (NAC) resulted abrogation EMT stemness cells, indicating role nicotine-induced ROS these morphological changes. result controls through regulation AKT pathway during early stages carcinogenesis. Additionally, epigenetic regulatory altered nicotine-exposed cells reversed by NAC. therapeutics 5-aza-2'-deoxycytidine Trichostatin A abrogated stemness. This oxidative stress caused alterations contributing transformation. To our knowledge, first report showing ROS-mediated modifications as mechanism further potential pharmacological intervention cancer.