%0 Journal Article
%T Alterations in the homeostasis of phospholipids and cholesterol by antitumor alkylphospholipids
%A Jos¨¦ M Jim¨¦nez-L¨®pez
%A Pablo R¨ªos-Marco
%A Carmen Marco
%A Josefa L Segovia
%A Mar¨ªa P Carrasco
%J Lipids in Health and Disease
%D 2010
%I BioMed Central
%R 10.1186/1476-511x-9-33
%X Alkylphospholipid (APL) derivatives are novel cytostatic agents that, in contrast to most of the currently used chemotherapeutic drugs, do not target DNA or the cytoskeleton but act at the cell membrane [1]. There is increasing interest in the biological activity of these lipid analogs as they selectively inhibit the growth of transformed cells and could well complement existing DNA-directed anticancer chemotherapies. Miltefosine (hexadecylphosphocholine) belongs to the alkylphosphocholine (APC) group, which exert antitumor activity against a broad spectrum of established tumor cell lines and solid tumors [2-5]. The inhibition of tumor cell proliferation caused by these agents may be the result not only of direct cell damage but also because of the induction of apoptosis [6]. Initial clinical studies have shown promising results; for example, miltefosine may be used for the topical treatment of cutaneous metastases of mammary carcinomas [7]. Remarkably, miltefosine exhibits potent leishmanicidal activity as a consequence of its interference with the parasite's metabolic pathways [8]; thus, orally administered miltefosine has been reported to be efficacious against the visceral and cutaneous forms of leishmaniasis [9,10]. Miltefosine is also toxic in vitro to other protozoan parasites [11-13].Miltefosine is a representative member of a second generation of the synthetic APL family, being the prototype of the first generation edelfosine. In an attempt to improve antitumor activity with reduced side effects, erucylphosphocholine and perifosine appeared (Figure 1). Compared to miltefosine, erucylphosphocholine contains a longer hydrocarbon chain with a cis double bond and perifosine presents a piperidine moiety instead of the choline head group [1]. A wide variety of molecular mechanisms have been proposed to explain the antitumor activity of distinct membrane-directed APLs [14], whose action appears to depend on the cell type [15], the uptake rate into the cell [16] an
%U http://www.lipidworld.com/content/9/1/33