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

Biochem Biophys Res Commun. 2013 Aug 23;438(2):312-7. doi: 10.1016/j.bbrc.2013.07.067. Epub 2013 Jul 24.


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.

Keywords: Apoptosis; Glioma; Hv1; Voltage-gated proton channel; Zn(2+).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis*
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Survival
  • Chlorides / pharmacology
  • Female
  • Glioma / metabolism*
  • Humans
  • Hydrogen-Ion Concentration
  • Ion Channels / antagonists & inhibitors*
  • Ion Channels / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Zinc / pharmacology*
  • Zinc Compounds / pharmacology


  • Antineoplastic Agents
  • Chlorides
  • Hv1 channel, human
  • Ion Channels
  • Zinc Compounds
  • zinc chloride
  • Zinc