Activation of Cellular Pathway by Nickel Nanoparticles May Trigger Lung Cancer

Brown University researchers have discovered that nickel nanoparticles trigger a cellular pathway called HIF-1 alpha that leads to cancer in human lung cells.

The Chair of the Department of Pathology and Laboratory Medicine in Brown University’s The Warren Alpert Medical School, Agnes Kane and senior author of the research along with her team of engineers, chemists and pathologists discovered that ions on the surface of the nickel nanoparticles are dispersed into human epithelial lung cells to activate a HIF-1 alpha pathway, which usually activates genes that provide cell support during hypoxia, a condition of low oxygen supply. However, the pathway also supports the growth of tumor cells.

She also stated that nickel uses the HIF-1 alpha pathway by causing the cell to believe that there is hypoxia but actually the pathway is activated by a nickel ion. The activation of this pathway may allow premalignant tumor cells to grow, she said.

Jodie Pietruska, first author and postdoctoral research associate led the research team. During the study, the research team allowed human lung cells to react with microscale metallic nickel particles and nanoscale particles of nickel oxide and metallic nickel. The team observed that the microscale metallic nickel particles were less problematic, while the nanoscale particles triggered the HIF-1 alpha pathway. The nanoparticles are chemically more reactive than microscale particles due to their larger surface area, Kane said.

The researchers also observed that the cells exposed to nickel oxide particles died rapidly, leaving no chance for cancer to grow, while metallic nickel particles were less effective to kill the cells, allowing cancer to develop. Pietruska stated that what is worrying is the sustained activation caused by the metallic nickel nanoparticles although they were mildly cytotoxic.


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