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1.
In Vivo ; 32(4): 765-770, 2018.
Article in English | MEDLINE | ID: mdl-29936457

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.


Subject(s)
Cell Differentiation/drug effects , Neoplasms/drug therapy , Neurons/drug effects , Topoisomerase Inhibitors/adverse effects , Animals , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Camptothecin/pharmacology , Doxorubicin/adverse effects , Doxorubicin/pharmacology , Drug Resistance, Neoplasm/drug effects , Drug Screening Assays, Antitumor , Etoposide/adverse effects , Etoposide/pharmacology , Humans , Irinotecan , Neoplasms/pathology , PC12 Cells , Rats , Topoisomerase Inhibitors/therapeutic use
2.
In Vivo ; 32(2): 231-239, 2018.
Article in English | MEDLINE | ID: mdl-29475904

ABSTRACT

BACKGROUND/AIM: We have previously reported the protection of doxorubicin-induced keratinocyte toxicity by alkaline extract of the leaves of Sasa senanensis Rehder (SE). In order to extend the generality of the cell protective effect of SE, we investigated whether it also protects rat PC12 and human SH-SY5Y neuron model cells from amyloid ß-peptide (Aß)-induced injury. MATERIALS AND METHODS: Viability of cells was determined by the MTT method. Cytotoxicity was evaluated by the concentration that reduces the cell viability by 50% (CC50). Protection from Aß-induced cytotoxicity was evaluated by the concentration that reversed the Aß-induced reduction of viability by 50% (EC50). The selectivity index (SI) of neuroprotective activity was defined as the ratio of EC50 to CC50 Aß1-42 aggregation was assayed using Aß1-42 ammonium hydroxide. RESULTS: SE showed hormetic growth stimulation at lower concentrations in both neuron precursors and differentiated cells. SE reproducibly inhibited Aß-induced cytotoxicity against both undifferentiated and differentiated neuron cells. Both the extent of differentiation induction and viability depended on the cell density, suggesting the release of growth and differentiation stimulation substances into culture supernatant. Higher concentrations of SE partially reduced the Aß1-42 aggregation. CONCLUSION: Hormetic growth stimulation and inhibition of aggregation may be involved in the neuroprotective activity of SE.


Subject(s)
Amyloid beta-Peptides/metabolism , Neurons/drug effects , Neurons/metabolism , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Plant Leaves/chemistry , Sasa/chemistry , Amyloid beta-Peptides/pharmacology , Animals , Antioxidants/pharmacology , Cell Differentiation/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Humans , Neurons/pathology , Protein Aggregates/drug effects , Protein Aggregation, Pathological/metabolism , Rats
3.
In Vivo ; 31(6): 1089-1095, 2017.
Article in English | MEDLINE | ID: mdl-29102930

ABSTRACT

BACKGROUND/AIM: Most of the previous investigators have used various types of media for the culture of nerve cells. In order to optimize the culture conditions, we compared the growth rate and amino acid consumption by two popular neuron models, rat PC12 and human SH-SY5Y, grown in DMEM or DMEM: Ham's F-12 (1:1): non-essential amino acids, supplemented with 10% fetal bovine serum (referred to DMEM and Mix, respectively). MATERIALS AND METHODS: Cell growth was monitored by the MTT method. Amino acids in the culture medium were quantitated by amino acid analysis after deproteinization. RESULTS: Efficient cell attachment could be achieved even if PC12 cells were inoculated at extreme lower cell density in a non-coated plain dish, without addition of its condition medium. Both PC12 and SH-SY5Y cells proliferated up to slightly higher cell density in DMEM than in Mix. Approximately 2-fold higher utilization rate of glutamine and essential amino acids was observed in DMEM. Amyloid peptides such as Aß1-42 and Aß25-35 suppressed their growth nearly by 50%. CONCLUSION: The present study suggests the usefulness of DMEM for the study of searching neuroprotective substances, based on its favorable effects on cell attachment, cell growth and amino acid utilization as well as amyloid peptide sensitivity.


Subject(s)
Amino Acids/isolation & purification , Cell Proliferation/genetics , PC12 Cells/chemistry , Amino Acids/genetics , Animals , Cell Survival/genetics , Cells, Cultured , Culture Media/chemistry , Humans , Neurons/chemistry , Neurons/metabolism , PC12 Cells/metabolism , Rats
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