Change in Anticancer Drug Sensitivity During Neuronal Differentiation of PC12 Cells
| Autor: | Yaeko Hara, Tadayoshi Kaneko, Tomoyuki Abe, Takahiro Kaneko, Hiroshi Shiratsuchi, Mika Nakagawa, Hiroshi Takeshima, Haixia Shi, Hayato Suzuki, Kenta Tanaka, Soichi Iwama, Nobuaki Tamura, Norio Horie, Hiroshi Sakagami |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Topoisomerase Inhibitors medicine.drug_class Cellular differentiation Cell Pharmacology Irinotecan PC12 Cells Neuroprotection General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Neoplasms medicine Animals Humans Viability assay Cytotoxicity Etoposide Neurons Chemistry Neurotoxicity Cell Differentiation medicine.disease Rats 030104 developmental biology medicine.anatomical_structure Doxorubicin Drug Resistance Neoplasm Camptothecin Drug Screening Assays Antitumor Topoisomerase inhibitor Research Article medicine.drug |
| Zdroj: | In Vivo. 32:765-770 |
| ISSN: | 1791-7549 0258-851X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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