Fluvoxamine alleviates paclitaxel-induced neurotoxicity
| Autor: | Hitoshi Tanimukai, Takashi Kudo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Paclitaxel
CACI chemotherapy-associated cognitive impairments Biophysics Sig-1R sigma 1 receptor Caspase 4 Caspase 3 CHOP Pharmacology CHOP C/EBP homologous protein Biochemistry BIX BiP inducer X ER endoplasmic reticulum UPR unfolded protein response Medicine Viability assay JNK c-Jun NH2-terminal kinase SSRI selective serotonin reuptake inhibitor Sigma-1 receptor biology business.industry Px paclitaxel Neurotoxicity Antagonist Flv fluvoxamine medicine.disease Selective serotonin reuptake inhibitor QOL quality of life Fluvoxamine Unfolded protein response biology.protein Endoplasmic reticulum stress CYP cytochrome P450 Sigma 1 receptor BiP immunoglobulin heavy-chain binding protein business Chemobrain Research Article |
| Zdroj: | Biochemistry and Biophysics Reports |
| ISSN: | 2405-5808 |
| Popis: | Paclitaxel (Px) is an effective chemotherapeutic agent for the treatment of various cancers. However, it is often associated with neurological side effects, including chemotherapy-associated cognitive impairment (CACI), such as “chemobrain”. Previously, we reported that endoplasmic reticulum (ER) stress is involved in Px-induced neurotoxicity, and immunoglobulin heavy chain binding protein (BiP) inducer X (BIX) alleviates Px-induced neurotoxicity. However, BIX has not been used in clinical practice yet. We recently reported that fluvoxamine (Flv) alleviates ER stress via induction of sigma-1 receptor (Sig-1R). The purpose of this study was to investigate whether Flv could alleviate Px-induced neurotoxicity in vitro. SK-N-SH cells were pre-treated for 12 h with or without 10 μg/ml Flv followed by treatment with 1 μM Px with or without co-existence of 10 μg/ml Flv for 24 h. To investigate the involvement of Sig-1R in alleviation effect on Px-induced neurotoxicity,1 μM NE100, an antagonist of Sig-1R, was added for 24 h. Neurotoxicity was assessed using the MTS viability assay and ER stress-mediated neurotoxicity was assessed by evaluating the expression of C/EBP homologous protein (CHOP), cleaved caspase 4, and cleaved caspase 3. Pre-treatment with Flv significantly alleviated the induction of CHOP, cleaved caspase 4, and cleaved caspase 3 in SK-N-SH cells. At the same time, pre-treatment with Flv significantly induced Sig-1R in SK-N-SH cells. In addition, viability was significantly higher in Flv-treated cells than in untreated cells, which was reversed by treatment with NE100. Our results suggest that Flv alleviates Px-induced neurotoxicity in part through the induction of Sig-1R. Our findings should contribute to one of the novel approaches for the alleviation of Px-induced neurotoxicity, including chemobrain. Highlights • Paclitaxel (Px) induces neurotoxicity through endoplasmic reticulum (ER) stress. • Fluvoxamine (Flv) alleviates Px-induced ER-mediated neurotoxicity. • Sigma1 receptor is involved in alleviation of Px-induced neurotoxicity. • Flv could be a candidate drug for Px-induced neurological side effects. |
| Databáze: | OpenAIRE |
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