title: Cyclodextrin-induced apoptosis in human keratinocytes is caspase-8 dependent and accompanied by mitochondrial cytochrome c release.
abstract: Cyclodextrins (CDs) are cyclic oligosaccharides that are able to form inclusion complexes with a variety of substances. For pharmaceutical applications, CD-based drug formulations offer important advantages compared with uncomplexed drugs. These include improved water solubility of lipophilic drug molecules, increased chemical stability, as well as enhanced bioavailability and absorption rate. Also, a number of topical formulations for dermal and transdermal drug delivery contain CDs. However, the most frequently used CDs - beta-CD and MbetaCD - are known to extract cholesterol from plasma membranes and thus to cause cellular damage and cell death. In the present study, the influence of various CDs and CD derivatives on the human keratinocyte cell line HaCaT was assessed. We found that beta-CD and MbetaCD induce apoptosis via the activator caspase-8, which subsequently activates the effector caspases-3/-7. Furthermore, beta-CD-induced apoptosis is accompanied by mitochondrial cytochrome c release. A significant shift from mitochondria into the cytosol was found. These findings may provide further rationale to the use of CDs in topical formulations for dermal and transdermal drug delivery or as raw material in order to functionalize textiles for medical applications.
authors.affiliation: Department of Dermatology, Friedrich Schiller University of Jena, Jena, Germany. ute.schoenfelder@med.uni-jena.de
authors.forename: Ute
authors.initials: U
authors.lastname: Schönfelder
authors.forename: Anja
authors.initials: A
authors.lastname: Radestock
authors.forename: Peter
authors.initials: P
authors.lastname: Elsner
authors.forename: Uta-Christina
authors.initials: UC
authors.lastname: Hipler
mesh_terms: D000279:Administration, Cutaneous; D017209:Apoptosis / Q000187:drug effects; D053181:Caspase 8 / Q000378:metabolism*; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D005434:Flow Cytometry; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008928:Mitochondria / Q000201:enzymology; D047392:beta-Cyclodextrins / Q000494:pharmacology*
chemical_list: D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D045304:Cytochromes c; C505530:CASP8 protein, human; D053181:Caspase 8; C031215:betadex