黑色素瘤
青蒿琥酯
下调和上调
药理学
氧化应激
活力测定
血红素加氧酶
体内
癌细胞
毒性
细胞毒性
癌症研究
化学
体外
癌症
医学
生物
血红素
免疫学
酶
生物化学
恶性疟原虫
内科学
疟疾
基因
生物技术
有机化学
作者
Finn Jochims,Rebecca Strohm,Claudia von Montfort,Catharina Wenzel,Niklas P. Klahm,Arun Kumar Kondadi,Wilhelm Stahl,Andreas S. Reichert,Peter Brenneisen
出处
期刊:Biomedicines
[MDPI AG]
日期:2023-08-27
卷期号:11 (9): 2393-2393
标识
DOI:10.3390/biomedicines11092393
摘要
Despite great efforts to develop new therapeutic strategies to combat melanoma, the prognosis remains rather poor. Artesunate (ART) is an antimalarial drug displaying anti-cancer effects in vitro and in vivo. In this in vitro study, we investigated the selectivity of ART on melanoma cells. Furthermore, we aimed to further elucidate the mechanism of the drug with a focus on the role of iron, the induction of oxidative stress and the implication of the enzyme heme oxygenase 1 (HO-1). ART treatment decreased the cell viability of A375 melanoma cells while it did not affect the viability of normal human dermal fibroblasts, used as a model for normal (healthy) cells. ART’s toxicity was shown to be dependent on intracellular iron and the drug induced high levels of oxidative stress as well as upregulation of HO-1. Melanoma cells deficient in HO-1 or treated with a HO-1 inhibitor were less sensitive towards ART. Taken together, our study demonstrates that ART induces oxidative stress resulting in the upregulation of HO-1 in melanoma cells, which subsequently triggers the effect of ART’s own toxicity. This new finding that HO-1 is involved in ART-mediated toxicity may open up new perspectives in cancer therapy.
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