Effect of Sigma-1 Receptors on Voltage-Gated Sodium Ion Channels in Colon Cancer Cell Line SW620

Background: Voltage-gated sodium channels (VGSCs) play pivotal roles in the metastatic process in several cancers, including breast and colon cancers. Sigma-1 receptors are known to interact and form complexes with a number of ion channels aiding the delivery of the channel protein to the plasma membrane. Drugs that bind the Sigma-1 receptor are hypothesized to affect this process and reduce the delivery of the channel protein to the plasma membrane, in turn reducing the metastatic potential of the cells. Methods: Human colon cancer cell line SW620 was utilized as a model to investigate the interaction between the neonatal VGSC (nNav1.5) and the Sigma-1 receptor. This was accomplished using drugs that bind the Sigma-1 receptor, Sigma-1 receptor silencing, and antibodies that bind and block the nNav1.5 channel. Results: Sigma-1 receptor drugs SKF10047 and dimethyl tryptamine were found to alter (reduce) the adhesion of these cells by 46–54% at a 20 μM drug concentration. In a similar manner, gene silencing of the Sigma-1 receptor had a similar effect in reducing the adhesion of these cells to collagen-coated plates by 30%. The Sigma-1 receptor was found to be in a complex with nNav1.5 in SW620 cells, and Sigma-1 drugs or gene silencing of the Sigma-1 receptor results in a reduction of the surface expression of nNav1.5 by ∼50%. Culture of SW620 cells under hypoxic conditions resulted in upregulation of the Sigma-1 receptor and nNav1.5. In addition, surface expression of nNav1.5 protein increased under hypoxic culture conditions and this was inhibited by the application of SKF10047. Conclusions: It is proposed that in colon cancer cells, upregulated Sigma-1 receptor expression in hypoxia led to increased nNav1.5 protein expression at the plasma membrane and resulted in the cells switching to a more invasive state

Urinary Levoglucosan as a Biomarker for Wood Smoke: Results of Human Exposure Studies

Urinary levoglucosan was investigated as a potential biomarker for wood smoke exposure in two different controlled experimental settings. Nine subjects were exposed to smoke from a campfire in a controlled setting and four were exposed to smoke from an older model wood stove. All subjects were asked to provide urine samples before and after exposure, and to wear personal PM2.5 monitors during the exposure. Urinary levoglucosan measurements from both studies showed no consistent response to the smoke exposure. A third experiment was conducted to assess the contribution of dietary factors to urinary levoglucosan levels. Nine subjects were asked to consume caramel and provide urine samples before and after consumption. Urinary levoglucosan levels increased within 2 hours of caramel consumption and returned to pre-exposure levels within 24 hours. These studies suggest that diet is a major factor in determining urinary levoglucosan levels and recent dietary history needs to be taken into account for future work involving levoglucosan as a biomarker of wood smoke exposure