Phytochemicals represent an important source of novel anticancer and chemotherapeutic agents. Thymoquinone (TQ) is the major bioactive phytochemical derived from the seeds of Nigella sativa and has shown potent anticancer activities. In this study, we aimed to investigate the anticancer activity of Thymoquinone on the human renal carcinoma cell 786-O-SI3 and the underlying mechanism. By using cell proliferation assay, wound healing, and invasion assay, we found that Thymoquinone did not affect the viability of 786-O-SI3 and human kidney-2, but clearly inhibited the migration and invasion of 786-O-SI3. Further zymography and immunoblotting analysis showed that Thymoquinone downregulated the activity and expression of matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA) and attenuated the adhesion of 786-O-SI3 to type I and type IV collagen. Kinase cascade assay indicated that Thymoquinone inhibited the phosphorylation of phosphatidylinositol 3-kinase, Akt, Src, and Paxillin. In addition, Thymoquinone also decreased the level of fibronectin, N-cadherin, and Rho A. In parallel, Thymoquinone dose-dependently suppressed the transforming growth factor (TGF)-β-promoted u-PA activity and expression, as well as the cell motility and invasion of 786-O-SI3. Furthermore, tumor xenograft model revealed that Thymoquinone in vivo inhibited the 786-O-SI3 metastasizing to the lung. Collectively, these findings indicate that Thymoquinone inhibits the metastatic ability of 786-O-SI3, suggesting that Thymoquinone might be beneficial to promote the chemotherapy for renal cell carcinoma.

Thymoquinone is a phytochemical compound isolated from Nigella sativa and has various biological effects, including anti‐inflammation, antioxidation, and anticancer. Here, we further investigated the anticancer effects and associated molecular mechanism of 2‐methyl‐5‐isopropyl‐1,4‐benzoquinone (thymoquinone) on human renal carcinoma cell lines 786‐O and 786‐O‐SI3 and transitional carcinoma cell line BFTC‐909. Results showed that thymoquinone significantly reduced cell viability, inhibited the colony formation of renal cancer cells, and induced cell apoptosis and mitochondrial membrane potential change in both cancer cells. In addition, thymoquinone also triggered the production of reactive oxygen species (ROS) and superoxide and the activation of apoptotic and autophagic cascade. ROS inhibition suppressed the caspase‐3 activation and restored the decreased cell viability of 786‐O‐SI3 in response to thymoquinone. Autophagy inhibition did not restore the cell viability of 786‐O‐SI3 suppressed by thymoquinone. Moreover, thymoquinone suppressed the cell sphere formation and the expression of aldehyde dehydrogenase, Nanog, Nestin, CD44, and Oct‐4 in 786‐O‐SI3 cells. The tumor‐bearing model showed that thymoquinone in vivo inhibited the growth of implanted 786‐O‐SI3 cell. All these findings indicate that thymoquinone inhibits the proliferation of 786‐O‐SI3 and BFTC‐909 cell possibly due to the induction of ROS/superoxide and the consequent apoptosis, suggesting that thymoquinone may be a potential anticancer supplement for genitourinary cancer.

This study investigated the risk of insomnia and hypnotics use among emergency physicians. This cross-sectional study recruited physicians working in Taiwanese hospitals in 2015 and the general population as the participants. Data from 1,097 emergency physicians obtained from the National Health Insurance Research Database were grouped into the case group, whereas 14,112 nonemergency physicians and 4,388 people from the general population were categorized into the control groups. This study used logistic regression and conditional logistic regression to compare the risks of insomnia between emergency and nonemergency physicians and between emergency physicians and the general population, respectively. The prevalence of insomnia among emergency physicians, nonemergency physicians and general population was 5.56%, 4.08%, and 1.73%, respectively. Compared with nonemergency physicians and the general population, emergency physicians had a significantly higher risk of insomnia. The proportions of emergency physicians, nonemergency physicians, and general population using hypnotics were 19.96%, 18.24%, and 13.26%, respectively. Among emergency physicians who used hypnotics, 49.77%, 25.57%, and 24.66% used only benzodiazepines, only nonbenzodiazepines, and both benzodiazepines and nonbenzodiazepines, respectively. Nonpharmacological interventions to improve insomnia and reminder of safe use of hypnotics to emergency physicians can serve as references for hospitals in developing health-promoting activities.