Arsonoliposomes: effect of arsonolipid acyl chain length and vesicle composition on their toxicity towards cancer and normal cells in culture

Arsonolipid-containing liposomes were investigated in order to characterize the influence of the lipid acyl-chain length and liposome composition on cytotoxicity. Three types of cancer cells (HL-60, C6 and GH3), and two types of normal cells (HUVEC and RAME) were used. Liposomes containing the lauroyl, myristoyl and stearoyl side chain arsonolipids (with different lipid compositions) were incubated with a given number of cells and cell viability was estimated (MTT assay and trypan blue exclusion). Morphological studies were also performed in some cases. In addition, the interaction between some of the prepared arsonoliposomes and HUVEC cells was assessed. Results reveal that all the studied arsonoliposomes cause a dose dependent inhibition Of Survival in all three malignant cell lines studied (initiated at 10(-6) M). The corresponding toxicity against normal cells (HUVEC and RAME) is much lower for all arsonoliposomes, except for the lauroyl side chain arsonoliposomes which were demonstrated to be relatively toxic towards normal cells, especially RAME. The microscopic observations that these vesicles possibly cause apoptosis of most cell types studied, as well as the different speed of their cytotoxic activity, imply a different mechanism of action for this arsonoliposome type. Taking the results of this study in conjunction with our previous results on arsonoliposome physical stability and cytotoxicity, it is recommended that palmitoyl-arsonolipid arsonoliposomes be used for further investigations in vivo towards the development of an anticancer product. (C) 2002 Elsevier Science B.V. All rights reserved.