Calcium Channel Blockers: Inhibitors of Tumor Cell-Platelet-Endothelial Cell Interactions

The movement of calcium ions across cellular membranes (e. g., plasma membrane, endoplasmic or sarcoplasmic reticulum) can serve as a molecular messenger that modulates biochemical processes appropriate to the specific cell type. Calcium antagonists by preventing release of Ca2+ from intracellular stores, by peventing influx of external Ca2+ or by inhibiting the effects of Ca2+ through interactions with Ca2+-binding proteins such as calmodulin can interfere with these biochemical functions. The primary action of one subgroup of calcium antagonists is to interact with the channels in the cell membrane through which calcium enters the cells. This class of compounds originally described by Fleckenstein has been called by a variety of names including Ca2+-channel blockers, Ca2+-entry blockers, Ca2+-channel inhibitors and slow-channel blockers (for review see 1–3). We will use the terminology calcium channel blockers (CCB) in this chapter.