Diclofenac inhibits proliferation but not NGF-induced differentiation of PC12 cells.
Diclofenac is a non-steroidal anti-inflammatory drug that is prescribed for treatment of rheumatic diseases and as an analgesic. Although the information about these side effects has been widely reported, little is know about the effect of diclofenac on the neural cells. In this study, we investigated the effects of diclofenac on the proliferation and differentiation of PC12 cells. The cell proliferation was evaluated by using XTT assay in the both free-serum neurobasal medium supplemented with B27 supplement and DMEM/F12 medium containing 10% FBS. The nerve growth factor (NGF)-induced differentiation was assessed by measuring the neurite length. The drug toxicity was exhibited at the concentrations more than 310 microM in the supplemented neurobasal medium. The treatment of cells in the DMEM/F12 medium increased their sensitivity to diclofenac, with 40% and 75% growth inhibition at the 155 and 310 microM concentrations, respectively. The NGF-induced differentiation was not reduced by toxic and subtoxic concentrations of diclofenac. The results of this study indicated that diclofenac may be able to exhibit its neurotoxic effects through growth inhibition, but not differentiation inhibition. Supplement of B27 has several antioxidant compounds. Therefore, the difference of diclofenac cytotoxic effects in two culture media suggest that drug cytotoxicity may be related to the oxidative stress.
Rajabalian
Saeed
S
Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran. srajabalian@yahoo.com
Meimandi
Manzumeh Shamsi
MS
Badinloo
Marziyeh
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002642:Chick Embryo; D004008:Diclofenac / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D020932:Nerve Growth Factor