Low concentrations of curcumin induce growth arrest and apoptosis in skin keratinocytes only in combination with UVA or visible light.
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.
Dujic
Jadranka
J
Department of Dermatology and Venerology, Medical School, J.W. Goethe-University, Frankfurt/Main, Germany.
Kippenberger
Stefan
S
Hoffmann
Stephanie
S
Ramirez-Bosca
Ana
A
Miquel
Jaime
J
Diaz-Alperi
Joquin
J
Bereiter-Hahn
Jürgen
J
Kaufmann
Roland
R
Bernd
August
A
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
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