Action of vinca alkaloides on calcium movements through mitochondrial membrane.

The antimitotic drugs Vinblastine and Vincristine partially counteract the decoupling effect of both calcium ionophore and Ca2+ on mitochondria. The partial restoration of respiratory control is mainly due to an action on oxidative rate in state 4. In the same manner the P/O ratio is partially restorated. Moreover Vinca alkaloides decrease both the calcium uptake rate and its amount into mitochondria during aerobiosis and slacken the calcium efflux. These results may be explained by a non specific effect of Vinca alkaloides on mitochondrial membrane and might lead to a change in cytoplasmic Ca2+ concentration. Recently, calcium influx blockers (calcium antagonists) have appeared to enhance the cytotoxicity of Vinca alkaloides and to circumvent the Vincristine resistance of some tumor cells (Takashi Tsuruo et al. 1981, 1983). Besides, ruthenium red is a membrane inorganic dye known to bind and inhibit some calcium carriers (mitochondrial carrier, ATP ase calcium dependent from sarcoplasmic reticulum and erythrocyte). This dye has proved to increase the Vinblastine cell accumulation and its toxicity on cells culture (Wilberding C. 1984). So calcium might be involved in the therapeutic activity of Vinca alkaloides. Therefore, in order to investigate this possible implication we studied the effect of these drugs on calcium movements in mitochondria.