ID | 116249 |
著者 |
Li, Mengling
University of Toyama
Wu, Chengai
Institute of Orthopaedic Trauma
Muhammad, Jibran Sualeh
University of Sharjah
Yan, Dan
Capital Medical University
Hatta, Hideki
University of Toyama
Cui, Zheng-Guo
University of Toyama|University of Fukui
Inadera, Hidekuni
University of Toyama
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キーワード | Melatonin
SIRT3/SOD2
Apoptosis
Reactive oxygen species
AKT
Shikonin
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資料タイプ |
学術雑誌論文
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抄録 | Recent research suggests that melatonin (Mel), an endogenous hormone and natural supplement, possesses anti-proliferative effects and can sensitise cells to anti-cancer therapies. Although shikonin (SHK) also possesses potential anti-cancer properties, the poor solubility and severe systemic toxicity of this compound hinders its clinical usage. In this study, we combined Mel and SHK, a potentially promising chemotherapeutic drug combination, with the aim of reducing the toxicity of SHK and enhancing the overall anti-cancer effects. We demonstrate for the first time that Mel potentiates the cytotoxic effects of SHK on cancer cells by inducing oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway. Particularly, Mel-SHK treatment induced oxidative stress, increased mitochondrial calcium accumulation and reduced the mitochondrial membrane potential in various cancer cells, leading to apoptosis. This drug combination also promoted endoplasmic reticulum (ER) stress, leading to AKT dephosphorylation. In HeLa cells, Mel-SHK treatment reduced SIRT3/SOD2 expression and SOD2 activity, while SIRT3 overexpression dramatically reduced Mel-SHK-induced oxidative stress, ER stress, mitochondrial dysfunction and apoptosis. Hence, we propose the combination of Mel and SHK as a novel candidate chemotherapeutic regimen that targets the SIRT3/SOD2-AKT pathway in cancer.
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掲載誌名 |
Redox Biology
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ISSN | 22132317
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出版者 | Elsevier
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巻 | 36
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開始ページ | 101632
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発行日 | 2020-07-02
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権利情報 | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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言語 |
eng
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著者版フラグ |
出版社版
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部局 |
医学系
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