Dexmedetomidine Stimulates Cellular Senescence of Lung Cancer Cells Via NOX5.

Dexmedetomidine is a highly selective α- 2 adrenergic receptor agonist which has been considered as a promising anticancer agent. However, the underlying molecular mechanisms whereby Dexmedetomidine exerts its anticancer and chemopreventive actions need to be elucidated. In this study, we found that Dexmedetomidine reduced cell viability of the lung cancer cell line A549 cells in a dose-dependent manner. Importantly, Dexmedetomidine reduced the telomerase activity in A549 cells by reducing the gene levels of hTERT but increasing the gene levels of TERF2. The senescence- associated-β- galactosidase (SA-β-Gal) staining assay demonstrates that Dexmedetomidine stimulated cellular senescence by activating the p53/p16 signaling. Additionally, treatment with Dexmedetomidine led to increased ROS production and the expression of γH2AX, implicating typical DNA damage in lung cancer cells. Interestingly, Dexmedetomidine increased the expression of NOX5 but not NOX1 or NOX2. Knockdown of NOX5 abolished the effects of Dexmedetomidine in telomerase activity, gene expression of hTERT and TERF2, the p53/p16 signaling, as well as cellular senescence, suggesting that the effects of Dexmedetomidine are mediated by NOX5. In summary, these findings show that Dexmedetomidine blunts the growth of lung cancer cells by inducing premature senescence via ROS-mediated DNA damage.