title: N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, inhibits cell proliferation.
abstract: N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and its derivatives are putative calmodulin antagonists that bind to calmodulin and inhibit Ca2+/calmodulin-regulated enzyme activities. Autoradiographic studies using tritiated W-7 showed that this compound penetrates the cell membrane, is distributed mainly in the cytoplasm, and inhibits proliferation of Chinese hamster ovary K1 (CHO-K1) cells. Cytoplasmic [3H]W-7 was excluded completely within 6 hr after removal of [3H]W-7 from the culture medium. N-(6-aminohexyl)-1-naphthalenesulfonamide, an analogue of W-7 that interacts only weakly with calmodulin, proved to be a much weaker inhibitor of cell proliferation. CHO-K1 cells were synchronized by shaking during mitosis and then released into the cell cycle in the presence of 25 microM W-7 or 2.5 mM thymidine for 12 hr. Cell division was observed approximately 6 hr later. The results suggest that the effect of W-7 on cell proliferation might be through selective inhibition of the G1/S boundary phase, which is similar to the effect of excess thymidine. This pharmacological demonstration that cytoplasmic calmodulin is involved in cell proliferation is significant; W-7 and its derivatives may be useful tools for research on calmodulin and cell biology-related studies.
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003959:Diamines / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D010053:Ovary; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002135:Calcium-Binding Proteins; D002147:Calmodulin; D003959:Diamines; D013449:Sulfonamides; C017967:W 7; D002118:Calcium