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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
キーワード
Melatonin
SIRT3/SOD2
Apoptosis
Reactive oxygen species
AKT
Shikonin
資料タイプ
学術雑誌論文
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.
掲載誌名
Redox Biology
ISSN
22132317
出版者
Elsevier
36
開始ページ
101632
発行日
2020-07-02
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/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系