Experimental studies on topoisomerase inhibitor camptothecin as an antipsoriatic agent.
OBJECTIVE
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 of scale with granular layer per 100 scales in mouse tail epidermis were determined in vivo. Experiments on cultured normal human keratinocytes were performed using the methods of crystal violet staining, absorbance-cell number 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 differentiation by camptothecin were showed in animal models and were reconfirmed in cultured 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 aurintricarboxylic acid.


CONCLUSIONS
The therapeutic effects of camptothecin on psoriasis can at least partly be explained by its multiple effects on DNA as a topoisomerase inhibitor.
Lin
X
X
Department of Dermatology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. linxr@dlut.edu.cn
Wilkinson
D I
DI
Huang
T
T
Farber
E M
EM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004054:Diethylstilbestrol / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D051379:Mice; D011565:Psoriasis / Q000188:drug therapy*; D013623:Tail / Q000166:cytology; D059004:Topoisomerase I Inhibitors; D014621:Vagina / Q000166:cytology*
D059004:Topoisomerase I Inhibitors; D004054:Diethylstilbestrol; D002166:Camptothecin