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Inhibition of ATP-synthase potentiates cytotoxicity of combination drug menadione/ascorbate in leukaemia lymphocytes
https://repo.qst.go.jp/records/85034
https://repo.qst.go.jp/records/85034273c5760-d9fd-4bf3-b65a-9d98c641ccb2
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2022-01-07 | |||||
| タイトル | ||||||
| タイトル | Inhibition of ATP-synthase potentiates cytotoxicity of combination drug menadione/ascorbate in leukaemia lymphocytes | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Semkova, Severina
× Semkova, Severina× Ivanova, Donika× Nikolova, Biliana× Zlateva, Genoveva× Bakalova, Rumiana× Zhelev, Zhivko× Ichio, Aoki× Bakalova, Rumiana× Ichio, Aoki |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The combination drug menadione/ascorbate (M/A) manifests synergistic dose-dependent antiproliferative and cytotoxic effects towards cancer cells, but not towards normal cells of the same origin especially at concentrations that can be achieved in vivo by its oral and parenteral administration. It is assumed that M/A alters selectively dysfunctional cancerous mitochondria. However, the exact molecular mechanism is not clear yet. The aim of the present study was to elucidate the role of adenosine triphosphate (ATP) synthase activity and its suppression by oligomycin-A on M/A-induced cytotoxicity, mitochondrial superoxide and ATP level in leukaemic lymphocytes. Cells were treated with different concentrations of M/A in the absence and presence of oligomycin-A (100ng/mL) for 24h and 48h. The cell growth and viability, steady-state ATP level and mitochondrial superoxide were analysed using conventional analytical tests. The results showed that suppression of ATP synthase activity by oligomycin-A decreased the cell growth and viability and increased the production of mitochondrial superoxide and depletion of ATP in cells treated with low/tolerable doses of M/A (up to 5/500μM/μM), compared to the cells treated with M/A only. Oligomycin-A did not affect these parameters in cells treated with high doses of M/A (10/1000 and 20/2000μM/μM). The inhibition of ATP synthase potentiated the cytotoxicity of M/A, particularly in leukaemic lymphocytes treated with low/tolerable doses. We assume that the cytotoxicity of M/A is tightly connected to impairment of oxidative phosphorylation, and mitochondrial ATP depletion is a crucial factor for cell death. | |||||
| 書誌情報 |
Biotechnology & Biotechnological Equipment 巻 35, 号 1, p. 1738-1744, 発行日 2022-02 |
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| 出版者 | ||||||
| 出版者 | Taylor & Francis | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1310-2818 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1080/13102818.2021.1996268 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.tandfonline.com/doi/full/10.1080/13102818.2021.1996268 | |||||
