Experimental studies on topoisomerase inhibitor camptothecin as an antipsoriatic agent

Objectives To elucidate the therapeutic mechanism of topical camptothecin ( CPT) in treating psoriasis and to detect the effects of CPT on keratinocyte proliferation, differentiation and apoptosis. Methods Mitotic numbers in mouse vaginal epithelium at estrus and numbers o f scale with granular layer per 100 scales in mouse tail epidermis were det ermined in vivo. Experiments on cultured normal human keratinocytes were pe rformed using the methods of crystal violet staining, absorbance-cell numbe r converting. cell counting and quantitation of morphologic; changes during differentiation, transglutaminase assay and nucleosomal enrichment assay. Results Inhibition of cell proliferation and promotion of cell differentiat ion by camptothecin were showed in animal models and were reconfirmed in cu ltured keratinocytes. Apoptosis was induced by camptothecin and was showed by activation of "tissue" transglutaminase and increase in nucleosomes. The endonuclease activity was reduced by an endonuclease inhibitor aurintricar boxylic acid. Conclusion The therapeutic effects of camptothecin on psoriasis can at leas t: partly be explained by its multiple effects on DNA as a topoisomerase in hibitor.