title: Antitumor Lipids--Structure, Functions, and Medical Applications.
abstract: Cell proliferation and metastasis are considered hallmarks of tumor progression. Therefore, efforts have been made to develop novel anticancer drugs that inhibit both the proliferation and the motility of tumor cells. Synthetic antitumor lipids (ATLs), which are chemically divided into two main classes, comprise (i) alkylphospholipids (APLs) and (ii) alkylphosphocholines (APCs). They represent a new entity of drugs with distinct antiproliferative properties in tumor cells. These compounds do not interfere with the DNA or mitotic spindle apparatus of the cell, instead, they incorporate into cell membranes, where they accumulate and interfere with lipid metabolism and lipid-dependent signaling pathways. Recently, it has been shown that the most commonly studied APLs inhibit proliferation by inducing apoptosis in malignant cells while leaving normal cells unaffected and are potent sensitizers of conventional chemo- and radiotherapy, as well as of electrical field therapy. APLs resist catabolic degradation to a large extent, therefore accumulate in the cell and interfere with lipid-dependent survival signaling pathways, notably PI3K-Akt and Raf-Erk1/2, and de novo phospholipid biosynthesis. They are internalized in the cell membrane via raft domains and cause downstream reactions as inhibition of cell growth and migration, cell cycle arrest, actin stress fibers collapse, and apoptosis. This review summarizes the in vitro, in vivo, and clinical trials of most common ATLs and their mode of action at molecular and biochemical levels.
authors.affiliation: Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria. Electronic address: aneliakk@yahoo.com.
authors.forename: Aneliya
authors.initials: A
authors.lastname: Kostadinova
authors.affiliation: Faculty of Biology, Cytology, Histology and Embryology, Sofia University, Sofia, Bulgaria.
authors.forename: Tanya
authors.initials: T
authors.lastname: Topouzova-Hristova
authors.affiliation: Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Albena
authors.initials: A
authors.lastname: Momchilova
authors.affiliation: Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria. Electronic address: rtzoneva65@gmail.com.
authors.forename: Rumiana
authors.initials: R
authors.lastname: Tzoneva
authors.affiliation: German Cancer Research Center, Toxicology and Chemotherapy Unit, Heidelberg, Germany.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Berger
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D019869:Phosphatidylinositol 3-Kinases
keywords: Alkylphosphocholines; Apoptosis; Cell cycle arrest; Cell growth; Cytoskeleton alteration; Lipid rafts; Mechanism of action of antitumor lipids; Phospholipid metabolism; Phospholipid synthesis; Signal transduction