Chloramphenicol induces in vitro growth arrest and apoptosis of human keratinocytes.
Chloramphenicol (CAP) is a broad-spectrum antibacterial drug that is widely used for topical application in ophthalmology and dermatology. In the present study we investigated the influence of CAP on human keratinocyte proliferation and apoptosis in vitro. CAP significantly inhibited proliferation and induced apoptosis of cultivated human keratinocytes, as revealed by incorporation of radioactive thymidine and flow cytometry analysis of intracellular esterase activity in fluorescein diacetate-stained cells, respectively. CAP-induced keratinocyte apoptosis was associated with activation of caspases and increased production of reactive oxygen species. The pro-apoptotic action of CAP was antagonized by the antioxidant agent N-acetylcysteine, the protein synthesis inhibitor cycloheximide, and PD98059, a selective inhibitor of extracellular signal-regulated kinase (ERK) activation. Taken together, these data indicate that CAP inhibits keratinocyte proliferation through induction of oxidative stress and ERK-mediated caspase-dependent apoptosis.
Popadic
S
S
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Belgrade, Serbia and Montenegro.
Popadic
D
D
Ramic
Z
Z
Mostarica Stojkovic
M
M
Trajkovic
V
V
Milinkovic
M
M
Medenica
L
L
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002701:Chloramphenicol / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D002701:Chloramphenicol; D007770:L-Lactate Dehydrogenase; D020169:Caspases