Evaluation of antitumor effects of new antineoplastic phospholipids analogous an inhibitor of the enzyme CtP: phosphoethanolamine citidililtransferase in non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is therapeutically limited and despite the successful use of small molecule inhibitors there are many resistant patients to current chemotherapeutics, and this remains a major problem in the treatment of advanced disease. In this regard, it is of utmost a development of new useful compounds, efficient and selective that possibility the treatment of patients with lung cancer. An interesting and novel class of agents is the antineoplastic phospholipids that target the cell membrane by affecting its turnover leading to apoptosis induction with a highselectivity for tumor cells. Our group is engaged in the development of new CTP:phosphoethanolamine cytidylyltransferase inhibitors derivatives of antineoplastic phospholipids as novel and possible better antitumor agents. CTP:phosphoethanolamine cytidylyltransferase catalyzes a crucial step in phosphatidylethanolamine synthesis, known as the Kennedy pathway, and uses phophoethanolamine as a substrate. Inhibition of this enzyme results in cell cycle arrest and a topological impairment of the transmembrane protein domains, particularly those in mitochondria, lead to induction of apoptosis. Of note, enzymeinhibition affects the cellular bioenergetics and together with impaired lipids signaling is thought to trigger apoptosis. In the current study we will elucidate the more precise antitumor mechanism and apoptosis activation induced by antineoplasticphospholipids-analogous in NSCLC cell lines. In addition, an establish orthotopic mice model with A549-luc cells will be employed to study efficacy of the novel agents. (AU)