Alkyl ether lipids, ion channels and lipid raft reorganization in cancer therapy.
Synthetic alkyl lipids, such as the ether lipids edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and ohmline (1-O-hexadecyl-2-O-methyl-rac-glycero-3-β-lactose), are forming a class of antitumor agents that target cell membranes to induce apoptosis and to decrease cell migration/invasion, leading to the inhibition of tumor and metastasis development. In this review, we present the structure-activity relationship of edelfosine and ohmline, and we point out differences and similarities between these two amphiphilic compounds. We also discuss the mechanisms of action of these synthetic alkyl ether lipids (involving, among other structures and molecules, membrane domains, Fas/CD95 death receptor signaling, and ion channels), and highlight a key role for lipid rafts in the underlying process. The reorganization of lipid raft membrane domains induced by these alkyl lipids affects the function of death receptors and ion channels, thus leading to apoptosis and/or inhibition of cancer cell migration. The possible therapeutic use of these alkyl lipids and the clinical perspectives for these lipids in prevention or/and treatment of tumor development and metastasis are also discussed.
CEMCA, UMR CNRS 6521, IBSAM, Université de Brest, 6, Avenue V. Le Gorgeu, 29238 Brest Cedex 3, France; Network "Ion channels and Cancer-Canceropole Grand Ouest", (IC-CGO), France. Electronic address: http://www.ic-cgo.fr.
Paul-Alain
PA
Jaffrès
Laboratory of Cell Death and Cancer Therapy, Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), C/Ramiro de Maeztu 9, E-28040 Madrid, Spain.
Consuelo
C
Gajate
INSERM/University of Tours U1069, Nutrition-Croissance et Cancer (N2C), F-37032 Tours, France; Network "Ion channels and Cancer-Canceropole Grand Ouest", (IC-CGO), France. Electronic address: http://www.ic-cgo.fr.
Ana Maria
AM
Bouchet
CEMCA, UMR CNRS 6521, IBSAM, Université de Brest, 6, Avenue V. Le Gorgeu, 29238 Brest Cedex 3, France; Network "Ion channels and Cancer-Canceropole Grand Ouest", (IC-CGO), France. Electronic address: http://www.ic-cgo.fr.
Hélène
H
Couthon-Gourvès
INSERM/University of Tours U1069, Nutrition-Croissance et Cancer (N2C), F-37032 Tours, France; Network "Ion channels and Cancer-Canceropole Grand Ouest", (IC-CGO), France. Electronic address: http://www.ic-cgo.fr.
Aurélie
A
Chantôme
INSERM/University of Tours U1069, Nutrition-Croissance et Cancer (N2C), F-37032 Tours, France; Network "Ion channels and Cancer-Canceropole Grand Ouest", (IC-CGO), France. Electronic address: http://www.ic-cgo.fr.
Marie
M
Potier-Cartereau
INSERM/University of Tours U1069, Nutrition-Croissance et Cancer (N2C), F-37032 Tours, France; Network "Ion channels and Cancer-Canceropole Grand Ouest", (IC-CGO), France. Electronic address: http://www.ic-cgo.fr.
Pierre
P
Besson
INSERM/University of Tours U1069, Nutrition-Croissance et Cancer (N2C), F-37032 Tours, France; Centre HS Kaplan, CHU Bretonneau, Tours F-37032, France; Network "Ion channels and Cancer-Canceropole Grand Ouest", (IC-CGO), France. Electronic address: http://www.ic-cgo.fr.
Philippe
P
Bougnoux
Laboratory of Cell Death and Cancer Therapy, Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), C/Ramiro de Maeztu 9, E-28040 Madrid, Spain.
Faustino
F
Mollinedo
INSERM/University of Tours U1069, Nutrition-Croissance et Cancer (N2C), F-37032 Tours, France; Network "Ion channels and Cancer-Canceropole Grand Ouest", (IC-CGO), France. Electronic address: christophe.vandier@univ-tours.fr.
Christophe
C
Vandier
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D015195:Drug Design; D006017:Glycolipids / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010742:Phospholipid Ethers / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
C574297:1-O-hexadecyl-2-O-methylglycero-3-lactose; D000970:Antineoplastic Agents; D006017:Glycolipids; D007473:Ion Channels; D010742:Phospholipid Ethers; C026659:edelfosine
Alkyl ether lipids; Apoptosis; Cell migration; Death receptor; Ion channel; Lipid rafts