title: An investigation of the effects of dithranol-induced apoptosis in a human keratinocyte cell line.
abstract: OBJECTIVE
  Dithranol, one of the most successful topical agents for the treatment of psoriasis, has been shown to exert its therapeutic effect by inducing keratinocyte apoptosis. To gain further insights into dithranol-induced apoptotic events in vitro, a detailed investigation of its time- and dose-dependent effects has been performed through the evaluation of selected apoptotic markers, using a human keratinocyte cell line (HaCaT) as a model.
  
  
  METHODS
  The time- and dose-dependent effects of dithranol on a human keratinocyte cell line (HaCaT) were investigated through the evaluation of a series of apoptotic markers; morphological changes (electron microscopy), phosphatidylserine externalisation (flow cytometry), and caspase-3/7 activation.
  
  
  RESULTS
  The dithranol-induced apoptotic cascade was found to follow a well-defined dose and time-course, with the concentration and the period of exposure to the drug acting as the two major factors influencing the events and nature of cell death. The earliest apoptotic event detected was caspase activation (after 6 h), followed by the occurrence of phosphatidylserine externalisation (after 9 h) and subsequently the morphological characteristics associated with early and late stage apoptosis/necrosis (after 12 h).
  
  
  CONCLUSIONS
  This study has elucidated the dose- and time-response effects of dithranol-induced apoptosis in human keratinocytes in vitro.
authors.affiliation: Sunderland Pharmacy School, University of Sunderland, Sunderland, UK.
authors.forename: Suja E
authors.initials: SE
authors.lastname: George
authors.forename: Rosaleen J
authors.initials: RJ
authors.lastname: Anderson
authors.forename: Malcolm
authors.initials: M
authors.lastname: Haswell
authors.forename: Paul W
authors.initials: PW
authors.lastname: Groundwater
mesh_terms: D000875:Anthralin / Q000009:adverse effects / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D053179:Caspase 7 / Q000737:chemistry / Q000378:metabolism; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D003879:Dermatologic Agents / Q000009:adverse effects / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010718:Phosphatidylserines / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D013499:Surface Properties / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D003879:Dermatologic Agents; D010718:Phosphatidylserines; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D000875:Anthralin