Intracellular delivery of ceramide lipids via liposomes enhances apoptosis in vitro.

摘要: Abstract Ceramide lipids have emerged as important intracellular signalling molecules that mediate diverse cellular effects, of which programmed cell death, or apoptosis, has attracted significant interest. Although the exact mechanism(s) by ceramides trigger apoptosis is not fully understood, there considerable evidence they are key mediators this response. Exogenously applied, cell-permeable been shown to induce when incubated with cells in culture. We examined here cytotoxicity varying acyl chain lengths order determine whether length affects pro-apoptotic activity within concentration range 0–100 μM. found for C6-, C8-, C10-, C14- and C16-ceramide, was inversely proportional cytotoxic activity, C6-ceramide being most active (IC50 values 3–14 μM range) C16-ceramide least excess 100 μM) MDA435/LCC6 human breast cancer J774 mouse macrophage lines investigated. Using these two ceramide forms we were able correlate observed uptake, a lack delivery may be responsible weak C16-ceramide. therefore investigated possibility incorporating into liposome bilayers enhance delivery. demonstrate stable, ceramide-containing liposomes can formulated, taken up vitro. These results provide an increased understanding differences exogenous short- long-chain lipids, their incorporation biologically liposomal formulations opens new avenues induction.