Membrane cholesterol content and sensitivity of human carcinoma-cells to antineoplastic ether phospholipids

Ether phospholipids represent a new class of anti-cancer drugs which appear to exert their tumoricidal activity through a direct and indirect cytotoxic effect against tumor cells of different origins. The chemotherapeutic interest in these new drugs is based on the finding that, contrary to the majority of anti-cancer drugs, ether phospholipids do not interfere with DNA synthesis, are anti-invasive and induce tumor cell differentiation. There is increasing experimental evidence that the direct cytotoxic effect of these new drugs is mediated by the cell membrane. We have measured the lipid membrane composition of three human carcinoma cell lines that have been found to possess different sensitivity to the tumoricidal activity of four antitumor ether phospholipids. A statistically significant difference has been found in the membrane cholesterol content of the three cell lines and a positive correlation has been established between the membrane cholesterol level and the carcinoma cell sensitivity to ether phospholipids. These findings emphasize previous data obtained with leukemic cells and reinforce the interest in ether phospholipids whose cytotoxic properties may represent a new step towards a more promising anti-cancer chemotherapy.