title: Interaction of α-Hexylcinnamaldehyde with a Biomembrane Model: A Possible MDR Reversal Mechanism.
abstract: The ability of the naturally derived compound α-hexylcinnamaldehyde (1) to interact with biomembranes and to modulate their permeability has been investigated as a strategy to reverse multidrug resistance (MDR) in cancer cells. Dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLVs) were used as biomembrane models, and differential scanning calorimetry was applied to measure the effect of 1 on the thermotropic behavior of DMPC MLVs. The effect of an aqueous medium or a lipid carrier on the uptake of 1 by the biomembrane was also characterized. Furthermore, taking into account that MDR is strictly regulated by redox signaling, the pro-oxidant and/or antioxidant effects of 1 were evaluated by the crocin-bleaching assay, in both hydrophilic and lipophilic environments. Compound 1 was uniformly distributed in the phospholipid bilayers and deeply interacted with DMPC MLVs, intercalating among the phospholipid acyl chains and thus decreasing their cooperativity. The lipophilic medium allowed the absorption of 1 into the phospholipid membrane. In the crocin-bleaching assay, the substance produced no pro-oxidant effects in both hydrophilic and lipophilic environments; conversely, a significant inhibition of AAPH-induced oxidation was exerted in hydrophilic medium. These results suggest a possible role of 1 as a chemopreventive and chemosensitizing agent for fighting cancer.
authors.affiliation: †Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sarpietro
authors.affiliation: ‡Department of Physiology and Pharmacology "V. Erspamer", "Sapienza" University, P.le Aldo Moro 5, 00185 Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Sotto
authors.affiliation: §Department of Health Sciences, University Magna Græcia of Catanzaro, University Campus "S. Venuta", Viale Europa, 88100 Germaneto (CZ), Italy.
authors.forename: Maria Lorena
authors.initials: ML
authors.lastname: Accolla
authors.affiliation: †Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Castelli
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D018432:Drug Resistance, Multiple / Q000502:physiology*; D008954:Models, Biological; D015394:Molecular Structure; D010743:Phospholipids / Q000737:chemistry
chemical_list: D010743:Phospholipids; C551429:alpha-hexylcinnamaldehyde; D000171:Acrolein; D004134:Dimyristoylphosphatidylcholine