Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation

Yu, Xiang; Chen, Xiaying; Wang, Wengang; Zhai, Li; Sun, Xueni; Jiao, Feng; Duan, Ting; Zhang, Mingming; Pan, Ting; Yan, Lili; Jin, Tengchuan; Gao, Quan; Wen, Chengyong; Ma, Weirui; Liu, Wen‐Cheng; Wang, Deqiang; Wu, Qibiao; Xie, Tian; Sui, Xinbing

doi:10.3389/fphar.2021.775506

Cited by 63 publications

(43 citation statements)

References 16 publications

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“…Ferroptosis is a newly defined form of regulated cell death which has attracted great interest in the field of cancer research. In a recent study, erianin was reported to induce ferroptosis in bladder cancer cells via NRF2 (nuclear factor erythroid 2–related factor 2) inactivation ( Xiang et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology

Yan

Zhang

Liu

et al. 2022

Front. Mol. Biosci.

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Erianin is a major bisbenzyl compound extracted from Dendrobium chrysotoxum Lindl., an important traditional Chinese herb. In recent years, a growing body of evidence has proved the potential therapeutic effects of erianin on various cancers, including hepatoma, melanoma, non-small-cell lung carcinoma, myelogenous leukemia, breast cancer, and osteosarcoma. Especially, the pharmacological activities of erianin, such as antioxidant and anticancer activity, have been frequently demonstrated by plenty of studies. In this study, we firstly conducted a systematic review on reported anticancer activity of erianin. All updated valuable information regarding the underlying action mechanisms of erianin in specific cancer was recorded and summarized in this paper. Most importantly, based on the molecular structure of erianin, its potential molecular targets were analyzed and predicted by means of the SwissTargetPrediction online server (http://www.swisstargetprediction.ch). In the meantime, the potential therapeutic targets of 10 types of cancers in which erianin has been proved to have anticancer effects were also predicted via the Online Mendelian Inheritance in Man (OMIM) database (http://www.ncbi.nlm.nih.gov/omim). The overlapping targets may serve as valuable target candidates through which erianin exerts its anticancer activity. The clinical value of those targets was subsequently evaluated by analyzing their prognostic role in specific cancer using Kaplan-Meier plotter (http://Kmplot.com/analysis/) and Gene Expression Profiling Interactive Analysis (GEPIA) (http://gepia.cancer-pku.cn/). To better assess and verify the binding ability of erianin with its potential targets, molecular flexible docking was performed using Discovery Studio (DS). The valuable targets obtained from the above analysis and verification were further mapped to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway using the Database for Annotation, Visualization and Integrated Discovery (DAVID) (http://david.abcc.ncifcrf.gov/) to explore the possible signaling pathways disturbed/regulated by erianin. Furthermore, the in silico prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of erianin was also performed and provided in this paper. Overall, in this study, we aimed at 1) collecting all experiment-based important information regarding the anticancer effect and pharmacological mechanism of erianin, 2) providing the predicted therapeutic targets and signaling pathways that erianin might act on in cancers, and 3) especially providing in silico ADMET properties of erianin.

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Section: Resultsmentioning

confidence: 99%

Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology

Yan

Zhang

Liu

et al. 2022

Front. Mol. Biosci.

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“…The CASC19, AC090197.1, AC099850.3, AL033397.2, LINC00462, and B3GALT1-AS1were found to be upregulated in the high-risk group, indicating that all these markers were involved in the malignancy processes for KIRP sufferers and were cancer-promoting factors. The findings of the above-mentioned biomarker suggest for future work, but the concrete evidence that will be responsible for the synthesis of important transcription factors associated with ferroptosis regulation, such as Fin56, NRF2, and SFRS9 is insufficient [41][42][43], and is lacking, necessitating further exploration. The LNCTAM34A and AC024022.1 were found to be upregulated in the low-risk group, these genes were KIRP tumor suppressor genes.…”

Section: Discussionmentioning

confidence: 99%

Potential biomarkers for predicting the overall survival outcome of kidney renal papillary cell carcinoma: an analysis of ferroptosis-related LNCRNAs

Huang

Cai

et al. 2022

BMC Urol

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Background Kidney renal papillary cell carcinoma (KIRP) is a dangerous cancer, which accounts for 15–20% of all kidney malignancies. Ferroptosis is a rare kind of cell death that overcomes medication resistance. Ferroptosis-related long non-coding RNAs (LNCRNAs) in KIRP, remain unknown. Method We wanted to express how ferroptosis-related LNCRNAs interact with immune cell infiltration in KIRP. Gene set enrichment analysis in the GO and KEGG databases were used to explore gene expression enrichment. The prognostic model was constructed using Lasso regression. In addition, we also analyzed the modifications in the tumor microenvironment (TME) and immunological association. Result The expression of LNCRNA was closely connected to the ferroptosis, according to co-expression analyses. CASC19, AC090197.1, AC099850.3, AL033397.2, LINC00462, and B3GALT1-AS1 were found to be significantly increased in the high-risk group, indicating that all of these markers implicates the malignancy processes for KIRP patients and may be cancer-promoting variables. LNCTAM34A and AC024022.1 were shown to be significantly elevated in the low-risk group; these might represent as the KIRP tumor suppressor genes. According to the TCGA, CCR, and inflammation-promoting genes were considered to be significantly different between the low-risk and high-risk groups. The expression of CD160, TNFSF4, CD80, BTLA, and TNFRSF9 was different in the two risk groups. Conclusion LNCRNAs associated with ferroptosis were linked to the occurrence and progression of KIRP. Ferroptosis-related LNCRNAs and immune cell infiltration in the TME may be potential biomarkers in KIRP that should be further investigated.

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“…Huang qin, which is extracted from the roots of S. baicalensis Georgi (Scutellariae Radix), triggers ferroptosis in vitro and in vivo by increasing intracellular chelate iron enrichment and ROS accumulation through overexpression of ferritin heavy chain 1 (FTH-1) ( Kong et al, 2021 ). Erianin, a ferroptosis inducer, can promote ROS accumulation by inactivating nuclear factor E2-related factor (Nrf2) and GSH, thereby inducing ferroptosis in tumor cells ( Xiang et al, 2021 ).…”

Section: Potential Therapeutic Drugsmentioning

confidence: 99%

Ferroptosis: A new therapeutic target for bladder cancer

et al. 2022

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Bladder cancer (BC) is the most frequent type of urinary system cancer. The prognosis of BC is poor due to high metastasis rates and multidrug resistance. Hence, development of novel therapies targeting BC cell death is urgently needed. As a novel cell death type with strong antitumor potential, ferroptosis has been investigated by many groups for its potential in BC treatment. As an iron-dependent cell death process, ferroptosis is characterized by excessive oxidative phospholipids. The molecular mechanisms of ferroptosis include iron overload and the system Xc-GSH-GPX4 signaling pathway. A recent study revealed that ferroptosis is involved in the metastasis, treatment, and prognosis of BC. Herein, in this review, we comprehensively summarize the mechanism of ferroptosis, address newly identified targets involved in ferroptosis, and discuss the potential of new clinical therapies targeting ferroptosis in BC.

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Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation

Cited by 63 publications

References 16 publications

Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology

Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology

Potential biomarkers for predicting the overall survival outcome of kidney renal papillary cell carcinoma: an analysis of ferroptosis-related LNCRNAs

Ferroptosis: A new therapeutic target for bladder cancer

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