Identification of ferroptosis as a novel mechanism for antitumor activity of natural product derivative a2 in gastric cancer

Liu, Ying; Song, Zhenghua; Liu, Huan; Ma, Xubin; Wang, Wang; Yu, Ke; Xu, You-Kai; Yu, De‐Quan; Liu, Hong‐Min

doi:10.1016/j.apsb.2021.05.006

Cited by 58 publications

(40 citation statements)

References 32 publications

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“…When BDNF-AS expression was knocked down, ferroptosis was significantly increased. The morphological changes of mitochondria in GC cells were consistent with the findings of previous studies 29 , 43 , 44 . Thus, our results indicated that BDNF-AS expression was correlated with the ferroptosis of GC cells.…”

Section: Discussionsupporting

confidence: 92%

The lncRNA BDNF-AS/WDR5/FBXW7 axis mediates ferroptosis in gastric cancer peritoneal metastasis by regulating VDAC3 ubiquitination

Huang¹,

Xiang²,

Wu³

et al. 2022

Int. J. Biol. Sci.

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Ferroptosis is a novel form of cell death that is closely associated with the formation of many tumors. Our study focused on the mechanism by which long noncoding RNAs (lncRNAs) regulate ferroptosis in gastric cancer (GC) peritoneal metastasis (PM). We utilized lncRNA sequencing and protein profiling analysis to identify ferroptosis-associated lncRNAs and proteins. qRT-PCR was used to analyze the expression of BDNF-AS and FBXW7 in GC tissues and adjacent normal tissues. Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and coimmunoprecipitation (co-IP) assays were performed to investigate the interaction between BDNF-AS and its downstream targets. Finally, the function of BDNF-AS was validated in vivo . We demonstrated that BDNF-AS was highly expressed in GC and PM tissues. High BDNF-AS expression was positively related to GC progression and poor prognosis. Functionally, BDNF-AS overexpression protected GC cells from ferroptosis and promoted the progression of GC and PM. Mechanistically, BDNF-AS could regulate FBXW7 expression by recruiting WDR5, thus affecting FBXW7 transcription, and FBXW7 regulated the protein expression of VDAC3 through ubiquitination. Conclusively, our research demonstrated that the BDNF-AS/WDR5/FBXW7 axis regulates ferroptosis in GC by affecting VDAC3 ubiquitination. BDNF-AS might be a biomarker for the evaluation of GC prognosis and the treatment of GC.

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Section: Discussionsupporting

confidence: 92%

The lncRNA BDNF-AS/WDR5/FBXW7 axis mediates ferroptosis in gastric cancer peritoneal metastasis by regulating VDAC3 ubiquitination

Huang¹,

Xiang²,

Wu³

et al. 2022

Int. J. Biol. Sci.

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show abstract

“…For example, Jiyuan oridonin A (JDA) is isolated from the Chinese medicinal herb Rabdosia rubescens and has antitumor properties. A2, a novel derivative of JDA, has been found to decrease the expression of GPX4 and induce ferroptosis, ultimately decreasing the growth of GC cells [130]. Actinidia chinensis Planch.…”

Section: Effects Of Dietary Nutrients and Phytochemicals On Ferroptosis And Gastric Diseasesmentioning

confidence: 99%

Ferroptosis: A Double-Edged Sword in Gastrointestinal Disease

Liu

Xiao

2021

IJMS

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Ferroptosis is a novel form of regulated cell death (RCD) that is typically accompanied by iron accumulation and lipid peroxidation. In contrast to apoptosis, autophagy, and necroptosis, ferroptosis has unique biological processes and pathophysiological characteristics. Since it was first proposed in 2012, ferroptosis has attracted attention worldwide. Ferroptosis is involved in the progression of multiple diseases and could be a novel therapeutic target in the future. Recently, tremendous progress has been made regarding ferroptosis and gastrointestinal diseases, including intestinal ischemia/reperfusion (I/R) injury, inflammatory bowel disease (IBD), gastric cancer (GC), and colorectal cancer (CRC). In this review, we summarize the recent progress on ferroptosis and its interaction with gastrointestinal diseases. Understanding the role of ferroptosis in gastrointestinal disease pathogenesis could provide novel therapeutic targets for clinical treatment.

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“…And ferroptosis inducers may be a promising strategy for cancer treatment, especially for the eradication of malignancies that are residual or resistant to chemotherapy ( Shen et al, 2018 ; Liang et al, 2019 ; Mou et al, 2019 ; Toyokuni et al, 2020 ). However, few ferroptosis inducers have been reported for gastric cancer ( Liu et al, 2021 ; Mao et al, 2021 ; Zhao et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Ferroptosis Inducer for Gastric Cancer Treatment Using Drug Repurposing Strategy

Zhang

Gao

Niu

et al. 2022

Front. Mol. Biosci.

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Gastric cancer remains one of the major contributors to global cancer mortality, although there is no promising target drug in clinics. Hence, the identification of novel targeted drugs for gastric cancer is urgent. As a promising strategy for inducing ferroptosis for gastric cancer treatment, the ferroptosis inducer is a potential drug. Nevertheless, no ferroptosis inducer has entered clinics. So, our purpose was to identify a novel ferroptosis inducer for gastric cancer treatment using a drug repurposing strategy. Firstly, using a drug repurposing strategy with the aid of a commercialized compound library, HC-056456, a small molecule bioactive CatSper channel blocker, was characterized to inhibit the growth of gastric cancer line MGC-803. At the same time, this anti-proliferation effect can be blocked by ferrostatin-1, a ferroptosis inhibitor, indicating that HC-056456 is a ferroptosis inducer. Then, HC-056456 was identified to decrease GSH content via p53/SLC7A11 signaling pathway. Then Fe2+ and lipid peroxide were accumulated when cells were exposed to HC-056456. Finally, HC-056456 was found to suppress the growth of gastric cancer cells by increasing p53 and repressing SLC7A11 in vivo but not in the presence of ferrostatin-1. In sum, we systematically elucidate that HC-056456 exerts anti-gastric cancer effect by provoking ferroptosis in vitro and in vivo, suggesting its potential role in gastric cancer treatment.

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Identification of ferroptosis as a novel mechanism for antitumor activity of natural product derivative a2 in gastric cancer

Cited by 58 publications

References 32 publications

The lncRNA BDNF-AS/WDR5/FBXW7 axis mediates ferroptosis in gastric cancer peritoneal metastasis by regulating VDAC3 ubiquitination

The lncRNA BDNF-AS/WDR5/FBXW7 axis mediates ferroptosis in gastric cancer peritoneal metastasis by regulating VDAC3 ubiquitination

Ferroptosis: A Double-Edged Sword in Gastrointestinal Disease

Identification of a Novel Ferroptosis Inducer for Gastric Cancer Treatment Using Drug Repurposing Strategy

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