In Vitro Evaluation of Antiproliferative Potential of Calcium Channel Blockers in Human Tenon's Fibroblasts

Abstract

The calcium cation has been known to play a central and diverse role in the proliferation of numerous types of cells including fibroblasts. Therefore, it follows that calcium channel blockers (CCBs) may potentially inhibit fibroblast attachment and proliferation. The time and dose-related effects of five commonly used CCBs—verapamil, diltiazem, nicardipine, trifluoperazine, and dantrolene—on human Tenon's fibroblast attachment and proliferation were studied. Fibroblasts were incubated with different concentrations of each drug. To evaluate the effect of each drug on fibroblast attachment, cell density was quantified by Coulter counter and hexosaminidase assays after 24 hours of incubation. To evaluate the effect of each drug on fibroblast proliferation, cell density was quantified by Coulter counter, hexosaminidase, and3H-thymidine uptake assays on days 1, 3, and 7. Dantrolene had minimal effect, failing to cause even 20% inhibition at 10−5M, the highest concentration tested. Verapamil, diltiazem, nicardipine, and trifluoperazine all inhibited fibroblast attachment and proliferation. Trifluoperazine was the most potent inhibitor of attachment and proliferation withID50s in the 10−5Mrange. Verapamil, diltiazem, and nicardipine had similar potency in inhibiting attachment and proliferation withID50s in the 10−4Mrange. Because CCBs seem to inhibit fibroblast attachment and proliferation, future clinical studies may show that these agents reduce collagen production, scar formation, and bleb failure following glaucoma filtration surgery.