β-L-1,3-Dioxolane-Cytidine:A Novel Nucleoside ThatInhibits Proliferation andInduces Differentiation ofKeratinocytes in vitro

Abstract

β-L-1,3-Dioxolane-cytidine (L-(–)-OddC) is a novel L-nucleoside, and its antitumor activity is under investigation in clinical trials. To evaluate the potential of L-(–)-OddC for treating hyperproliferative diseases of the skin, we examined its activity in human keratinocytes in vitro. The dose of L-(–)-OddC that inhibited the rate of proliferation of keratinocytes by 50% was 50 nM. L-(–)-OddC was about as cytotoxic as 9-β-D-arabinofuranosylcytosine but was about 1,000 time more potent than 3′-azidothymidine. L-(–)-OddC caused irreversible growth arrest and induced differentiation of keratinocytes. L-(–)-OddC altered morphology, increased the cell size of keratinocytes and increased the expression of involucrin. These data suggest that L-(–)-OddC may have potential as a therapeutic agent against hyperproliferative skin diseases.