Apoptosis-independent alterations in membrane dynamics induced by curcumin.
Curcumin is a well-known natural compound with antiinflammatory properties. Its antiproliferative effect and ability to modulate apoptotic response are considered essential in cancer therapy. The physicochemical properties of curcumin suggest membranous localization, which prompted an investigation of the mechanisms of membrane disturbances evoked by curcumin. We chose the erythrocyte as a convenient model for studying membrane effects of curcumin and showed its nonspecific, apoptosis-independent way of action. Curcumin was found to expand the cell membrane, inducing echinocytosis. Changes in cell shape were accompanied by transient exposure of phosphatidylserine. Membrane asymmetry was recovered by the action of aminophospholipid translocase, which remained active in the presence of curcumin. Lipids rearrangements and drug partitioning caused changes of lipid fluidity. Such nonspecific effects of curcumin on cellular membranes would produce artifacts of apoptosis measurement, since several methods are based on membrane changes.
Jaruga
E
E
Department of Molecular Biophysics, University of Lodz, Lodz, Poland. karla@biol.uni-lodz.pl
Sokal
A
A
Chrul
S
S
Bartosz
G
G
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001777:Blood Coagulation / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D050356:Lipid Metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D009996:Osmotic Fragility / Q000187:drug effects; D010718:Phosphatidylserines / Q000494:pharmacology; D049294:Phospholipid Transfer Proteins; D013696:Temperature; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D008565:Membrane Proteins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D003474:Curcumin