Arsenite increases sialic acid levels on the cellular surface through the inhibition of sialidase activity

Chronic exposure to arsenic has been shown to induce carcinogenesis in multiple organs, but the mechanisms underlying the multi-organ carcinogenicity of arsenic remain unknown. We here examined whether arsenic affects the amount of sialic acid on the cellular surface of immortalized HaCaT cells rather than cancerous cells to clarify the process of arsenic-induced carcinogenesis, since sialic acid is known to assist cancer cells in suppressing attacks by natural killer (NK) cells. Our results indicated that exposure to arsenite (As(III)) increases the amounts of sialic acid on the cell surface of HaCaT cells. To elucidate the mechanisms underlying the increase in the levels of sialic acid on the cell surface by As(III) exposure, we measured the activities of sialyltransferase and sialidase in HaCaT cells exposed to As (III). The results showed there was no significant change in the silalyltransferase activity, and the sialidase activity was significantly inhibited by As(III) exposure. When we examined the mRNA levels of NEU1-4, the four types of sialidases identified in mammals after exposure to As(III), no significant change was observed. Furthermore, sialidase activity was significantly reduced in NEU1 siRNA-transfected HaCaT cells, which showed the highest mRNA levels among NEU1-4 in HaCaT cells. These results suggest that inhibition of NEU1-derived sialidase activity by exposure to As(III) resulted in an increase in the amounts of sialic acid on the cell surface.