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

Journal Article · Fri Aug 23 04:00:00 EDT 2013 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2013.07.067· OSTI ID:22242059

Wang, Yifan; Zhang, Shangrong

Highlights: •Hv1 is expressed in highly metastatic glioma cell. •Zn{sup 2+} ions induces apoptosis in highly metastatic glioma cells. •Zn{sup 2+} ions markedly inhibit proton secretion. •Zn{sup 2+} ions reduce the gelatinase activity. •Inhibition of Hv1 activity via Zn{sup 2+} ions can effectively retard the cancer growth. -- Abstract: In contrast to the voltage-gated K{sup +} 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 140 μM zinc chloride induces apoptosis in the human highly metastatic glioma cells. Zn{sup 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{sup 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{sup 2+} ions may be used as a potential anti-glioma drug for glioma therapy.

• OSTI ID: 22242059
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 438; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
DRUGS
GLIOMAS
IN VIVO
INHIBITION
METASTASES
MICE
POTASSIUM IONS
ZINC CHLORIDES
ZINC IONS