The influence of atracurium, cisatracurium, and mivacurium on the proliferation of two human cell lines in vitro

We tested the influence of atracurium and cisatracurium (final concentratio ns: 0, 0.96, 3.2, 9.6, 32, and 96 muM) on proliferation of human cells (hep atoma HepG2 cells and human umbilical vein endothelial cells) in vitro. In additional experiments, glutathione, N-acetylcysteine, or carboxyl esterase was added before the addition of either relaxant. The number of cells, cou nted after 72 h of incubation was expressed as a percentage of the mean cel l number in wells incubated without additives. Atracurium and cisatracurium progressively decreased cell proliferation in a concentration-dependent pa ttern. With human umbilical vein endothelial cells, atracurium or cisatracu rium (3.2 muM) decreased the cell count to 67.7 % (SD, 14.8%) and 50% (SD, 8.6%), respectively. Cell proliferation was not inhibited by mivacurium. Th e results were similar to those with HepG2 cells. Glutathione, N-acetylcyst eine, and carboxyl esterase partially reversed the effects of atracurium an d cisatracurium. When incubated in a buffer with glutathione, atracurium de creased the number of glutathione-sulfhydryl groups. The findings that atra curium and cisatracurium inhibit proliferation of human cell lines in vitro , but that mivacurium does not, and that this effect is alleviated by gluta thione and N-acetylcysteine, as well as by the carboxyl esterase, indicate that the inhibition may be caused by the reactive acrylate metabolites.