Activity of potassium channel-blockers in breast cancer.
BACKGROUND
Potassium ion (K+) channels are known to play a key role in breast cancer proliferation.


METHODS
We investigated the expression of Kv1.3 voltage-gated K+ channels in 60 human breast cancer specimens by immunohistochemistry. The effects of K+ channel-blockers on cellular proliferation were examined in vitro.


RESULTS
No immunostaining was observed in 4 normal human breast specimens. Eighteen (30%) breast cancer specimens showed high, 35 (58%) moderate and 7 (12%) low Kv1.3 staining in the epithelial compartment. Minoxidil (K+ channel-opener) stimulated growth of MCF-7 human breast cancer cells (maximal approximately 60% at 10 micrograms/mL). K+ channel-blockers, dequalinium and amiodarone, had marked inhibitory effects on MCF-7 proliferation (> 90% inhibition at 1.5 micrograms/mL). Importantly, amiodarone and dequalinium potentiated the growth-inhibitory effects of tamoxifen on human breast (MCF-7, MDA-MB-231) as well as prostate (PC3, MDA-PCA-2B) and colon (Colo320DM, SW1116) cancer cell lines.


CONCLUSIONS
Investigation of combination therapy with tamoxifen and K+ channel-blockers is warranted.
Abdul
Mansoor
M
Edward Via Virginia College of Osteopathic Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA.
Santo
Arben
A
Hoosein
Naseema
N
D000638:Amiodarone / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003868:Dequalinium / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008914:Minoxidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D015221:Potassium Channels / Q000096:biosynthesis; D013629:Tamoxifen / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013629:Tamoxifen; D008914:Minoxidil; D003868:Dequalinium; D000638:Amiodarone; D005905:Glyburide