title: Beta-L-1,3-dioxolane-cytidine: a novel nucleoside that inhibits proliferation and induces differentiation of keratinocytes in vitro.
abstract: beta-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-beta-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.
authors.affiliation: Department of Dermatology, Yale University and VA Connecticut Healthcare System, West Haven, Conn. 06516, USA. pschwartz@biomed.med.yale.edu
authors.forename: P M
authors.initials: PM
authors.lastname: Schwartz
authors.forename: J G
authors.initials: JG
authors.lastname: Haggerty
authors.forename: Y C
authors.initials: YC
authors.lastname: Cheng
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004148:Dioxolanes / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D011498:Protein Precursors / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D000964:Antimetabolites, Antineoplastic; D004148:Dioxolanes; D011498:Protein Precursors; D015215:Zidovudine; C032253:involucrin; C074908:troxacitabine; D003596:Cytosine