RRC ID 54014
Author Sakagami H, Hara Y, Shi H, Iwama S, Nakagawa M, Suzuki H, Tanaka K, Abe T, Tamura N, Takeshima H, Horie N, Kaneko T, Shiratsuchi H, Kaneko T.
Title Change in Anticancer Drug Sensitivity During Neuronal Differentiation of PC12 Cells.
Journal In Vivo
Abstract BACKGROUND/AIM:Although there are many reports of anticancer drug-induced neurotoxicity, most previous data have been derived from neuronal cell models grown in a variety of culture conditions. This has prevented accurate assessment of the potency of their neurotoxicity and of changes in drug sensitivity of neuronal cells during differentiation. In this study, a simple neuronal differentiation induction system was established and the relative potency of neurotoxicity of eight anticancer drugs was compared during neuronal cell differentiation.
MATERIALS AND METHODS:Rat PC12 cells were induced to differentiate into neuronal cells by 50 ng/ml nerve growth factor in serum-free Dulbecco's modified Eagle's medium, followed by overlay of fresh nutrients at day 3, without medium change. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.
RESULTS:During differentiation, PC12 cells became 1.1-to more than 10,000-fold resistant to anticancer drugs. Topoisomerase inhibitors (doxorubicin, SN-38, etoposide) were the most toxic to differentiated PC12 cells, followed by docetaxel, gefitinib, melphalan, 5-fluorouracil and methotrexate. Docetaxel showed the highest cytotoxicity against undifferentiated PC12 cells, but its cytotoxicity was dramatically reduced during differentiation.
CONCLUSION:The present study demonstrated considerable variation in the neurotoxicity of anticancer drugs during the cell differentiation process. The present simple assay system may be useful to search for neuroprotective substances.
Volume 32(4)
Pages 765-770
Published 2018-1-1
DOI 10.21873/invivo.11306
PII 32/4/765
PMID 29936457
PMC PMC6117783
MeSH Animals Camptothecin / adverse effects Camptothecin / analogs & derivatives Camptothecin / pharmacology Cell Differentiation / drug effects* Doxorubicin / adverse effects Doxorubicin / pharmacology Drug Resistance, Neoplasm / drug effects Drug Screening Assays, Antitumor Etoposide / adverse effects Etoposide / pharmacology Humans Irinotecan Neoplasms / drug therapy* Neoplasms / pathology Neurons / drug effects* PC12 Cells Rats Topoisomerase Inhibitors / adverse effects* Topoisomerase Inhibitors / therapeutic use
IF 1.541
Times Cited 3
Human and Animal Cells PC-12(RCB0009)