Retinoic acid differentiated SH-SY5Y human neuroblastoma cells: an in vitro model to assess drug neurotoxicity.
OBJECTIVE
To evaluate whether retinoic acid (RA) differentiated human neuroblastoma (HN) SH-SY5Y cells are a suitable and reliable model to test the neurotoxicity of chemotherapic drugs without the confusing effects of the neurotrophic factors commonly used to induce neuronal differentiation.


METHODS
Cultures of the SH-SY5Y cell line were exposed to RA to induce neuronal differentiation which was assessed by measuring the neurite length. The effect of increasing concentrations of cisplatin (CDDP) on neurite outgrowth was determined. Cyclophosphamide (CTX) was used as negative control.


RESULTS
CDDP induced a significant reduction in the mean neurite length in a dose dependent manner. The neurotoxic effect of CDDP was reversible. Cyclophosphamide did not induce changes in RA differentiated HN cells.


CONCLUSIONS
RA differentiated HN cells are sensitive to the neurotoxic effect of CDDP and the course of the changes is similar to that observed in clinical practice and in in vivo experimental models. Therefore, this model is proposed as a screening method to test the neurotoxicity of chemotherapy drugs and the possible effect of neuroprotectant molecules and drugs.
Istituto di Anatomia Umana, Sezione di Neuroanatomia, Milano, Italy.
G
G
Nicolini
M
M
Miloso
C
C
Zoia
A
A
Di Silvestro
G
G
Cavaletti
G
G
Tredici
D000970:Antineoplastic Agents / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002945:Cisplatin / Q000633:toxicity*; D003520:Cyclophosphamide / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009498:Neurotoxins; D014212:Tretinoin; D003520:Cyclophosphamide; D002945:Cisplatin