Zn(2+) induces apoptosis in human highly metastatic SHG-44 glioma cells, through inhibiting activity of the voltage-gated proton channel Hv1.

In contrast to the voltage-gated K(+) channels, the voltage-gated proton channel Hv1 contains a voltage-sensor domain but lacks a pore domain. Here, we showed that Hv1 is expressed in the highly metastatic glioma cell SHG-44, but lowly in the poorly metastatic glioma cell U-251. Inhibition of Hv1 activity by 140μM zinc chloride induces apoptosis in the human highly metastatic glioma cells. Zn(2+) ions markedly inhibit proton secretion, and reduce the gelatinase activity in the highly metastatic glioma cells. In vivo, the glioma tumor sizes of the implantation of the SHG-44 xenografts in nude mice that were injected zinc chloride solution, were dramatically smaller than that in the controlled groups. The results demonstrated that the inhibition of Hv1 activity via Zn(2+) ions can effectively retard the cancer growth and suppress the cancer metastasis by the decrease of proton extrusion and the down-regulation of gelatinase activity. Our results suggest that Zn(2+) ions may be used as a potential anti-glioma drug for glioma therapy.