Voltage-gated sodium ion channels in prostate cancer: expression and activity.
BACKGROUND
High levels of voltage-gated sodium channels (VGSCs) have been previously associated with the invasiveness of rat and human prostate cancer (Pca) cell lines.


METHODS
4 normal prostate and 80 clinical Pca specimens on a tissue microarray slide were examined by immunohistochemistry using anti-sodium channel (III-IV linker region) antibody. The effects of a VGSC-opener and VGSC-blockers on the in vitro proliferation of 4 human Pca cell lines was examined.


RESULTS
Fifty-five% (44 out of 80) Pca specimens showed higher VGSC levels compared to normal, with 14 (of 44) showing increased focal staining. VGSC-opener veratrine (1-50 microg/mL), increased growth of PC3, DU145, LNCaP and MDA-PCA-2B Pca cells. VGSC-blockers, flunarizine (IC50=2 microg/mL) and riluzole (IC50=10-30 microg/mL) caused dose-dependent growth-inhibition of all four cell lines. Western analysis of cell extracts showed VGSC-immunoreactivity in the 4 Pca cell lines.


CONCLUSIONS
Our results indicate increased expression of VGSCs in Pca and VGSC involvement in Pca growth.
Abdul
Mansoor
M
Rumbaugh-Goodwin Institute for Cancer Research, Plantation, Florida 33313, USA.
Hoosein
Naseema
N
D000728:Androgens / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005444:Flunarizine / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019782:Riluzole / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000096:biosynthesis / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014702:Veratrine / Q000494:pharmacology
D000728:Androgens; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019782:Riluzole; D014702:Veratrine; D005444:Flunarizine