title: Effects of the antipsoriatic  drug dithranol on E2A and caspase-9 gene expression in vitro.
abstract: Although  the precise causes of psoriasis remain to be elucidated, psoriasis has been  known as a disorder in which factors in the immune system, enzymes and other  biochemical substances that regulate skin cell division are functionally  imbalanced, thereby resulting in rapid proliferation of keratinocytes and  incomplete keratinization. The expression of candidate genes such as E2A and  caspase-9, which have been recognized to play a critical role in cellular  proliferation/differentiation and apoptosis, is of great interest. They may be  therapeutically targeted by the antipsoriatic drug, dithranol. We examined the  molecular effects of dithranol on the mRNA and protein expression levels of E2A  and caspase-9 in the HaCaT keratinocyte cell line. The HaCaT cells were treated  with 0-0.5 μg/mL  dithranol for 30 min. After dithranol was washed out, the HaCaT cells were  cultured for 2 h, and their total cellular RNA and proteins were isolated.  Quantitative real-time reverse transcriptase-polymerase chain reaction and  Western blot were performed to determine the mRNA and protein levels of these  two genes. We found that dithranol treatment in the range of 0.25-0.5 μg/mL slightly upregulated the mRNA  expression of E2A and caspase-9 approximately 1.5- and 1.2-fold, respectively.  However, undetectable change and minor downregulation of the protein expression  levels were observed for E2A and caspase-9, respectively. Consequently, these  genes appear not to be viable therapeutic targets for dithranol.
authors.affiliation: Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathumthani, Thailand. cronpirin@yahoo.com
authors.forename: C
authors.initials: C
authors.lastname: Ronpirin
authors.forename: T
authors.initials: T
authors.lastname: Tencomnao
mesh_terms: D000875:Anthralin / Q000494:pharmacology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003879:Dermatologic Agents / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D011565:Psoriasis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000875:Anthralin; D051792:Basic Helix-Loop-Helix Proteins; D053453:Caspase 9; D003879:Dermatologic Agents; D012333:RNA, Messenger; C407909:TCF3 protein, human; C506433:CASP9 protein, human