Induction of Ferroptosis by Shikonin in Gastric Cancer via the DLEU1/mTOR/GPX4 Axis.

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Yiying Wang, Midie Xu, Cheng Liu, Xin Wang, Xiaoyan Zhang, Weiqi Sheng, Xiaoyu Wang
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引用次数: 0

Abstract

Gastric cancer (GC) is the most prevalent cancer in Asia. Shikonin, one of the ingredients extracted from the roots of Lithospermum erythrorhizon, has been proven to be a necrosis inducer and has an antitumour effect on many cancers. We explored the mechanism of the antitumour effect of shikonin in GC. CCK8 and clonogenic assays were used to determine the effect of shikonin on the proliferation of GC cell lines. Shikonin could induce reactive oxygen species (ROS), lipid ROS, intracellular ferrous iron (Fe2+), and malondialdehyde (MDA) in GC. We also found that shikonin decreased the expression of GPX4 by suppressing GPX4 synthesis and decreasing ferritin. Furthermore, long noncoding RNA deleted in lymphocytic leukaemia 1 (DLEU1) is an oncogene in GC, and shikonin decreased DLEU1 expression in GC cells. Overexpression of DLEU1 eliminated the anticancer effect of shikonin. Mechanistically, shikonin might decrease GPX4 levels by inhibiting the DLEU1/mTOR pathway. DLEU1 was sponged with miR-9-3p, which also regulated mTOR and GPX4. A xenograft tumour model of GC was established, and shikonin treatment inhibited cell proliferation and induced ferroptosis. In conclusion, shikonin exerts its antitumour effects on GC by triggering ferroptosis, and the DLEU1/mTOR/GPX4 axis may play an essential role in shikonin-induced ferroptosis. Therefore, our findings provide a potential lead compound for treating GC.

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来源期刊
Cell Biology International
Cell Biology International 生物-细胞生物学
CiteScore
7.60
自引率
0.00%
发文量
208
审稿时长
1 months
期刊介绍: Each month, the journal publishes easy-to-assimilate, up-to-the minute reports of experimental findings by researchers using a wide range of the latest techniques. Promoting the aims of cell biologists worldwide, papers reporting on structure and function - especially where they relate to the physiology of the whole cell - are strongly encouraged. Molecular biology is welcome, as long as articles report findings that are seen in the wider context of cell biology. In covering all areas of the cell, the journal is both appealing and accessible to a broad audience. Authors whose papers do not appeal to cell biologists in general because their topic is too specialized (e.g. infectious microbes, protozoology) are recommended to send them to more relevant journals. Papers reporting whole animal studies or work more suited to a medical journal, e.g. histopathological studies or clinical immunology, are unlikely to be accepted, unless they are fully focused on some important cellular aspect. These last remarks extend particularly to papers on cancer. Unless firmly based on some deeper cellular or molecular biological principle, papers that are highly specialized in this field, with limited appeal to cell biologists at large, should be directed towards journals devoted to cancer, there being very many from which to choose.
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