Alkyl Lysophospholipids in Cancer Treatment: Their Cytostatic and Immunomodulatory Role

New aza derivatives of the natural occurring 2-lysophosphatidylcholine have been synthetized and characterized for their antitumor and immunomodulatory activity. The cytotoxic and cytostatic effects have been studied on diverse human tumor cell lines. Flow cytometric analyses have revealed that the new aza-alkyl lysophospholipids (AALP) do not interfere with the S- and the M- phase of the cell cycle. In addition, the stathmokinetic analysis has pointed out a significant accumulation of tumoral cells in the G1 phase and a slow-down of the progression from late-S to G2 resulting in a block in this latter phase of the cell cycle. The immunomodulatory effect of the new AALP has also been studied. It has been found that these compounds markedly increased the tumor necrosis factor (TNF) production induced by lipopolysaccharide. In contrast, the AALP by themselves had no effect on the spontaneous release of TNF. These results indicate that AALP are able to kill cancer cells via a direct and indirect effect (i.e. immunomodulation) and thus they may constitute a new and original class of anticancer drugs.