title: Low concentrations of curcumin induce growth arrest and apoptosis in skin keratinocytes only in combination with UVA or visible light.
abstract: It is well known that curcumin, a dietary pigment from the plant Curcuma longa, inhibits cell proliferation and induces apoptosis in different cell lines at concentrations ranging from 10 to 150 microM (3.7-55 microg/ml). In this study, we show that curcumin at low concentrations (0.2-1 microg/ml) also has an antiproliferative effect when applied in combination with UVA or visible light. We demonstrate that such a treatment induces apoptosis in human skin keratinocytes represented by the increase of fragmented cell nuclei, release of cytochrome c from mitochondria, activation of caspases-9 and -8, and inhibition of NF-kappaB activity. Furthermore, inhibition of extracellular regulated kinases 1/2 and protein kinase B was found to ensure the proapoptotic effect. Additionally, the EGFR, an upstream regulator of both kinases, was inhibited indicating that apoptosis is induced by blocking survival- and proliferation-associated signal cascades at the receptor level. In summary, these findings suggest a new therapeutic concept for the treatment of hyperproliferative diseases by combining topical curcumin with UVA or visible light. In particular, the latter avoids the use of carcinogenic irradiation that is part of regular phototherapy.
authors.affiliation: Department of Dermatology and Venerology, Medical School, J.W. Goethe-University, Frankfurt/Main, Germany.
authors.forename: Jadranka
authors.initials: J
authors.lastname: Dujic
authors.forename: Stefan
authors.initials: S
authors.lastname: Kippenberger
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Ana
authors.initials: A
authors.lastname: Ramirez-Bosca
authors.forename: Jaime
authors.initials: J
authors.lastname: Miquel
authors.forename: Joquin
authors.initials: J
authors.lastname: Diaz-Alperi
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bereiter-Hahn
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.forename: August
authors.initials: A
authors.lastname: Bernd
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003474:Curcumin / Q000493:pharmacokinetics / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species; D014466:Ultraviolet Rays
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases; D003474:Curcumin