論文 - 詳細
| RRC ID | 54117 |
|---|---|
| 著者 | Hara Y, Sakagami H, Shi H, Abe T, Tamura N, Takeshima H, Horie N, Kaneko T, Shiratsuchi H, Kaneko T. |
| タイトル | Partial Protection of Paclitaxel-induced Neurotoxicity by Antioxidants. |
| ジャーナル | In Vivo |
| Abstract |
BACKGROUND/AIM:In order to search for substances that reduce the neurotoxicity of paclitaxel, the sensitivity of differentiated rat neuronal PC12 cells to paclitaxel was compared to that of malignant and non-malignant cells, and the extent to which four antioxidants can alleviate paclitaxel-induced neurotoxicity was investigated. MATERIALS AND METHODS:Viability of cells was determined by the MTT method. Cytotoxicity was evaluated as the concentration that reduced cell viability by 50% (CC50). Tumor specificity of paclitaxel was determined as the ratio of CC50 against non-malignant cells to that against malignant cells. RESULTS:Paclitaxel was three-fold more cytotoxic towards human oral squamous cell carcinoma cell lines (Ca9-22, HSC-2, HSC-3. HSC-4) than human normal epithelial and mesenchymal (human gingival fibroblast, human periodontal ligament fibroblast, human pulp cell) normal cells, confirming its antitumor potential. However, paclitaxel at as low a concentration as 5 ng/ml significantly reduced neurite formation in nerve growth factor-induced differentiated PC12 cells, although complete killing of cells was not achieved even at 2,000-fold higher concentration (10 μM). Paclitaxel-induced neurotoxicity was enhanced with the prolongation of incubation time and reduction of inoculation cell density. Four antioxidants, namely docosahexaenoic acid, acetyl-L-carnitine hydrochloride, N-acetyl-L-cysteine and sodium ascorbate, only partially protected PC12 cells from paclitaxel-induced toxicity. CONCLUSION:The present study suggests the involvement of both oxidative and other mechanisms in paclitaxel-induced neurotoxicity. |
| 巻・号 | 32(4) |
| ページ | 745-752 |
| 公開日 | 2018-1-1 |
| DOI | 10.21873/invivo.11303 |
| PII | 32/4/745 |
| PMID | 29936454 |
| PMC | PMC6117766 |
| MeSH | Animals Antioxidants / pharmacology Ascorbic Acid / pharmacology Carcinoma, Squamous Cell / complications* Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / pathology Cell Differentiation / drug effects Cell Survival / drug effects Cisplatin / adverse effects HL-60 Cells Humans Mouth Neoplasms / complications* Mouth Neoplasms / drug therapy Mouth Neoplasms / pathology Nerve Growth Factor / genetics Neurites / drug effects* Neurites / pathology Neurotoxicity Syndromes / etiology Neurotoxicity Syndromes / pathology Neurotoxicity Syndromes / prevention & control* PC12 Cells Paclitaxel / adverse effects Rats |
| IF | 1.541 |
| 引用数 | 3 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) |