Effects of voltage-gated ion channel modulators on rat prostatic cancer cell proliferation: Comparison of strongly and weakly metastatic cell lines

BACKGROUND. The strongly metastatic MAT-LyLu and the weakly metastatic AT-2 rat prostatic cancer cell lines have been shown to express voltage-gated i on channels differentially. In the present study, the possible contribution of voltage-gated ion channel activity to the proliferation of these cell l ines was investigated, in a comparative approach. METHODS. Several voltage-gated ion channel modulators were tested for their effects on proliferation over 54 hr, using an in vitro assay. The modes of action of the chemicals were monitored by electrophysiological (patch-clam p) recording. RESULTS. The voltage-gated K+ channel blockers C-aminopyridine (4-AP; 2 mM) , marga-toxin (5 nM), charybdotoxin (4.5 nM), and verapamil (50 mu M) inhib ited the K+ channels of both cell lines by between 38-65% and reduced the p roliferation of the AT-2 cell line, in a dose-dependent manner, by 8-51%. H owever, only 4-AP reduced proliferation of the MAT-LyLu cell line. Tetrodot oxin (6 mu M) blocked completely the voltage-gated Na+ channel expressed se lectively in the MAT-LyLu cell line, but had no effect on the proliferation of either cell line. On the other hand, the presumed Na+ channel "opener" veratridine (10-50 mu M) reduced significantly, in a dose-dependent manner, the proliferation of both cell lines by up to similar to 30%. CONCLUSIONS. We conclude that the mechanism(s) controlling the proliferatio n of the weakly metastatic AT-2 cells involves voltage-gated K+ channels. I n contrast, the proliferation of strongly metastatic MAT-LyLu cells is much less dependent upon voltage-gated K+ channel activity. (C) 2000 Wiley-Liss , Inc.