論文 - 詳細
| RRC ID | 78751 |
|---|---|
| 著者 | Bakalova R, Lazarova D, Sumiyoshi A, Shibata S, Zhelev Z, Nikolova B, Semkova S, Vlaykova T, Aoki I, Higashi T. |
| タイトル | Redox-Cycling "Mitocans" as Effective New Developments in Anticancer Therapy. |
| ジャーナル | Int J Mol Sci |
| Abstract |
Our study proposes a pharmacological strategy to target cancerous mitochondria via redox-cycling "mitocans" such as quinone/ascorbate (Q/A) redox-pairs, which makes cancer cells fragile and sensitive without adverse effects on normal cells and tissues. Eleven Q/A redox-pairs were tested on cultured cells and cancer-bearing mice. The following parameters were analyzed: cell proliferation/viability, mitochondrial superoxide, steady-state ATP, tissue redox-state, tumor-associated NADH oxidase (tNOX) expression, tumor growth, and survival. Q/A redox-pairs containing unprenylated quinones exhibited strong dose-dependent antiproliferative and cytotoxic effects on cancer cells, accompanied by overproduction of mitochondrial superoxide and accelerated ATP depletion. In normal cells, the same redox-pairs did not significantly affect the viability and energy homeostasis, but induced mild mitochondrial oxidative stress, which is well tolerated. Benzoquinone/ascorbate redox-pairs were more effective than naphthoquinone/ascorbate, with coenzyme Q0/ascorbate exhibiting the most pronounced anticancer effects in vitro and in vivo. Targeted anticancer effects of Q/A redox-pairs and their tolerance to normal cells and tissues are attributed to: (i) downregulation of quinone prenylation in cancer, leading to increased mitochondrial production of semiquinone and, consequently, superoxide; (ii) specific and accelerated redox-cycling of unprenylated quinones and ascorbate mainly in the impaired cancerous mitochondria due to their redox imbalance; and (iii) downregulation of tNOX. |
| 巻・号 | 24(9) |
| 公開日 | 2023-5-8 |
| DOI | 10.3390/ijms24098435 |
| PII | ijms24098435 |
| PMID | 37176145 |
| PMC | PMC10179378 |
| MeSH | Adenosine Triphosphate / metabolism Animals Ascorbic Acid / metabolism Mice Neoplasms* / metabolism Oxidation-Reduction Quinones / metabolism Superoxides* / metabolism |
| IF | 4.556 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Jurkat(RCB0806) |