title: Zn(2+) induces apoptosis in human highly metastatic SHG-44 glioma cells, through inhibiting activity of the voltage-gated proton channel Hv1.
abstract: 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.
authors.affiliation: Department of Biophysics, School of Physics Science, Nankai University, Tianjin 300071, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Wang
authors.forename: Shangrong
authors.initials: S
authors.lastname: Zhang
authors.forename: Shu Jie
authors.initials: SJ
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002712:Chlorides / Q000494:pharmacology; D005260:Female; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002712:Chlorides; C510235:HVCN1 protein, human; D007473:Ion Channels; D017967:Zinc Compounds; C016837:zinc chloride; D015032:Zinc
keywords: Apoptosis; Glioma; Hv1; Voltage-gated proton channel; Zn(2+)