Diclofenac inhibits proliferation and differentiation of neural stem cells.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in clinical situations as anti-inflammatory, analgesic and antipyretic drugs. However, it is still unknown whether NSAIDs have effects on the development of the central nervous system. In the present study, we investigated the effects of NSAIDs on neural stem cell (NSC) proliferation and differentiation into neurons. In contrast to aspirin, naproxen, indomethacin and ibuprofen, treatment with diclofenac (10 microM) for 2 days induced the death of NSCs in a concentration-dependent manner. Diclofenac also inhibited the proliferation of NSCs and their differentiation into neurons. Treatment with diclofenac resulted in nuclear condensation (a morphological change due to apoptosis of NSCs) 24hr after the treatment and activated caspase-3 after 6 hr, indicating that diclofenac may cause apoptosis of neuronal cells via activation of the caspase cascade. These results suggest that diclofenac may affect the development of the central nervous system.
Kudo
Chiho
C
Department of Pharmacology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
Kori
Maya
M
Matsuzaki
Kiyomi
K
Yamai
Kenshiki
K
Nakajima
Atsushi
A
Shibuya
Atsuhito
A
Niwa
Hitoshi
H
Kamisaki
Yoshinori
Y
Wada
Koichiro
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004008:Diclofenac / Q000494:pharmacology*; D004789:Enzyme Activation; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D020169:Caspases