| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2024-05-08 |
| タイトル |
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タイトル |
Docosahexaenoic acid potentiates the anticancer effect of the menadione/ascorbate redox couple by increasing mitochondrial superoxide and accelerating ATP depletion |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Ivanova D
Semkova S
Yaneva Z
Nicolova B
Zhivko Zhelev
Rumiana Bakalova
Aoki Ichio
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Background/Aim: Mitochondria-targeted anticancer drugs (“mitocans”) of natural origin are attractive candidates as adjuvants in cancer therapy. The redox couple menadione/ascorbate (M/A), which belongs to the “mitocane” family, induces selective oxidative stress in cancerous mitochondria and cells, respectively. The aim of this study was to elucidate the ability of docosahexaenoic acid (DHA) to potentiate the anticancer effect of M/A by increasing ROS production as well as affecting steady-state ATP levels in cancer cells. DHA has also been found to regulate the mevalonate pathway, which is closely related to the prenylation of the cytotoxic menadione to the non-cytotoxic menaquinone. Materials and Methods: The experiments were performed on leukemic lymphocyte Jurkat cells. Cells were treated with DHA, M/A, and their combination (M/A/DHA) and four parameters were examined using the following assays: cell viability and proliferation, steady-state ATP, mitochondrial superoxide, intracellular hydroperoxides. Three independent experiments with two or six parallel measurements were performed for each parameter. Results: The triple combination M/A/DHA was
characterized by much higher antiproliferative activity and cytotoxicity than M/A and DHA administered alone. DHA significantly accelerated M/A-induced ATP depletion in cells, which was accompanied by an additional increase in mitochondrial superoxide compared to cells treated with M/A or DHA alone. Conclusion: DHA significantly enhanced M/A- induced cytotoxicity in leukemic lymphocytes by inducing severe mitochondrial oxidative stress and accelerated ATP depletion. Selective DHA-mediated suppression of cholesterol synthesis in cancer cells (involved in the prenylation of cytotoxic menadione to the less cytotoxic phylloquinone), as well as DHA-mediated inhibition of superoxide dismutase are suggested to underlie the potentiation of the anticancer effect of M/A. |
| 書誌情報 |
Anticancer Research
巻 43,
号 3,
p. 1213-1220,
発行日 2023-03
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| 出版者 |
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出版者 |
International Institute of Anticancer Research (IIAR) |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1791-7530 |
| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
10.21873/anticanres.16268 |
