Voltage-gated potassium ion channels in colon cancer.
Voltage-gated potassium channels (VGPCs) have been previously implicated in cellular proliferation. In this study, the expression of VGPCs was examined by immunohistochemistry in seventy-four human colonic carcinoma specimens. Immunostaining for the Kv1.3 type VGPC was absent in two normal human colon specimens. Kv1.3 staining in the 74 colon cancer specimens was low in 9% (7/74), moderate in 61% (45/74) and high in 30% (22/74). Potassium channel (PC) openers, minoxidil and diazoxide (5-50 microg/ml), increased growth of SW1116, LoVo, Colo320DM and LS174t human colon cancer cell lines by 20-40%. PC-blockers, dequalinium and amiodarone, caused marked growth-inhibition of the four cell lines, at concentrations between 1 to 3 microg/ml. PC-blockers such as glibenclamide inhibited cellular proliferation at concentrations above 50 microg/ml while tetraethylammonium and 4-aminopyridine (up to 100 microg/ml) did not have significant growth-suppressive effects. Our results indicate the presence of VGPCs in colon cancer and suggest that PCs could serve as therapeutic targets.
Abdul
Mansoor
M
Rumbaugh-Goodwin Institute for Cancer Research, Plantation, FL 33313, USA.
Hoosein
Naseema
N
D015761:4-Aminopyridine / Q000494:pharmacology; D002455:Cell Division; D003110:Colonic Neoplasms / Q000378:metabolism*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D008914:Minoxidil / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D024642:Potassium Channels, Voltage-Gated; D014665:Vasodilator Agents; D008914:Minoxidil; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D003981:Diazoxide