Apoptosis induced by cationic liposome based on the mitochondrial signaling pathway in vitro.

Liposomes have been extensively applied in gene and drug delivery. It is indicated in many studies that cationic lipids possess a certain degree of cytotoxicity, primarily induced by the lipid head group. In this study, we investigated the cytotoxic mechanisms of peptide headgroup lipid (CDO14) and quaternary ammonium salt headgroup lipid (CDA14) on the NCI-H460 and MRC-5 cell lines. Both lipids were synthesized in our laboratory and with high transfection efficiency. The differences in changes of relevant proteins during the process of inducing cell apoptosis were compared at the cellular level between the two lipids. The results showed that both types of liposomes could lead to an increase in intracellular reactive oxygen species, a decrease in ATP content, a decrease in mitochondrial membrane potential, an increase in cytochrome c content, an increase in the BAX/BCL-2 ratio, and an increase in cleaved caspase-3 content. Among these changes, the variations in CDA14 were more significant than those in CDO14. Additionally, the cellular uptake of CDA14 was significantly higher than that of CDO14. These results suggested that the cytotoxicity of quaternary ammonium salt-based lipids was higher than that of peptide-based lipids. The cytotoxicity of cationic lipids is related to their head group structure, and their cytotoxic effect is mainly achieved by activating caspase-dependent endogenous apoptosis. [ABSTRACT FROM AUTHOR]