Comparative analyses of transcriptome sequencing and carcinogenic exposure toxicity of nicotine and 6-methyl nicotine in human bronchial epithelial cells

摘要

Electronic cigarettes have become a purported safer alternative to the conventional cigarettes in recent years. Nicotine is the main component of electronic cigarettes, and other nicotinic compounds are synthesized as al-ternatives to nicotine. However, scientific data on the potential health effects of electronic cigarettes are scarce. Herein, we evaluated the cytotoxicity of nicotine and its analog 6-methyl nicotine (6-MN) on human bronchial epithelial cells (BEAS-2B cells) in vitro. Furthermore, we performed transcriptome sequencing to systematically assess the effects of nicotine and 6-MN on BEAS-2B cells. The cytotoxicity assay revealed that BEAS-2B cells were more sensitive to 6-MN than to nicotine. Transcriptome sequencing revealed 1208 differentially expressed cancer-related proteins (CRP) in the 6-MN groups relative to that with CRP in the control group. In addition, 6-MN had a greater negative effect on the CRP expression than nicotine. Bioinformatic analysis revealed that the differentially expressed genes and proteins in the 6-MN group were significantly enriched in the cancer-related pathways, unlike those in the nicotine group. Further validations of some lung cancer-related proteins, such as NF-kappa B p65, EGFR, and MET, were conducted by immunoblotting and real-time PCR, which revealed that 6-MN may have a greater negative effect on tumor development and metastasis than nicotine. Taken together, our findings suggest that new electronic cigarettes with 6-MN might offer some advantages over conventional electronic cigarettes containing nicotine.

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