Bufotalin induces ferroptosis in non-small cell lung cancer cells by facilitating the ubiquitination and degradation of GPX4

Zhang, Wen; Jiang, Baoping; Liu, Yunxin; Xu, Lina; Wan, Meng

doi:10.1016/j.freeradbiomed.2022.01.009

Cited by 81 publications

(53 citation statements)

References 45 publications

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“…Despite the bumps along the way, an important breakthrough has been made that offers hope for the treatment of advanced gastric cancer patients; however, despite their impressive efficacy, treatment failure, drug resistance, and recurrence remain common [ 48 , 49 ]. Numerous studies have linked ferroptosis to the death of tumorigenic cells such as hepatocellular carcinoma, glioma, non-small cell lung cancer, and breast cancer [ 14 , 50 , 51 , 52 , 53 ]. As a result, targeting ferroptosis could be a novel approach to cancer treatment [ 54 ]; however, there are still relatively few studies on the role of ferroptosis in gastric cancer, especially the potential regulatory mechanisms in relation to TME characteristics, immunotherapy response, and prognosis, which remain to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

The Ferroptosis Molecular Subtype Reveals Characteristics of the Tumor Microenvironment, Immunotherapeutic Response, and Prognosis in Gastric Cancer

Zhou

Lan

et al. 2022

IJMS

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Ferroptosis is a relatively new form of programmed cell death, which can enhance the efficacy of tumor immunotherapy by regulating the tumor microenvironment (TME). In the face of the dilemma of a great difference in the efficacy of immunotherapy for gastric cancer (GC) patients, the exploration of ferroptosis may assist us in predicting immunotherapy efficacy prior to treatment. The potential role of ferroptosis in TME still needs further elucidation. Based on ferroptosis-related genes (FRGs), we systematically evaluated ferroptosis molecular subtypes in gastric cancer. Additionally, the association between these molecular subtypes and the characteristics of TME was examined. A ferroptosis score was constructed to further explore the predictive efficacy of ferroptosis on the immunotherapy response in gastric cancer. There were also 32 other cancers that were evaluated. Three molecular subtypes of ferroptosis in gastric cancer were identified. The three immunophenotypes of tumor immune inflamed, immune excluded, as well as immune desert were mostly in agreement with the TME features of these three subtypes. The individual tumor genetic variation, TME characteristics, immunotherapy response, and prognosis could be assessed by a ferroptosis score. High ferroptosis scores in gastric cancer suggest stromal activation and immunosuppression. It is noted that tumors with a low ferroptosis score are characterized by extensive tumor mutations as well as an immune activation, which are associated with an enhanced immunotherapy response and an improved prognosis. This study reveals that ferroptosis plays an integral role in the regulation of the tumor immune microenvironment. The ferroptosis score may serve as an independent prognostic factor for GC and will deepen our understanding of the TME infiltration mechanisms as well as lead to more rational immunotherapy regimens.

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Section: Discussionmentioning

confidence: 99%

The Ferroptosis Molecular Subtype Reveals Characteristics of the Tumor Microenvironment, Immunotherapeutic Response, and Prognosis in Gastric Cancer

Zhou

Lan

et al. 2022

IJMS

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“…A number of studies have proved that some natural compounds ( Table 1 ) such as dihydroartemisinin ( Yuan et al, 2020 ), artesunate ( Zhang Q. et al, 2021 ),sulforaphane ( Iida et al, 2021 ), curcumin ( Tang X. et al, 2021 ), bufotalin ( Zhang W. et al, 2022 ), sanguinarine ( Xu R. et al, 2022 ), sinapine ( Shao et al, 2022 ), solasonine ( Zeng et al, 2022 ), ophiopogonin B ( Zhang L. et al, 2022 ), red ginseng polysaccharide ( Zhai et al, 2022 ) Dihydroisotanshinone I ( Wu et al, 2021 ).inhibits the proliferation, colony formation and induces ferroptosis of lung cancer cells by the interfering mRNA and/or protein expression and/or degradation of SLC7A11 or GPX4. Apart from natural compounds, some drugs that have been marketed ( Table 1 ) such as Vorinostat ( Zhang T. et al, 2021 ), Orlistat ( Zhou W. et al, 2021 ) have also been found to act as ferroptosis inducers in lung cancer cells via inhibiting System X c − /GSH/GPX4 axis.…”

Section: Potential Roles Of Targeting System X C ...mentioning

confidence: 99%

System Xc−/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy

et al. 2022

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The activation of ferroptosis is a new effective way to treat drug-resistant solid tumors. Ferroptosis is an iron-mediated form of cell death caused by the accumulation of lipid peroxides. The intracellular imbalance between oxidant and antioxidant due to the abnormal expression of multiple redox active enzymes will promote the produce of reactive oxygen species (ROS). So far, a few pathways and regulators have been discovered to regulate ferroptosis. In particular, the cystine/glutamate antiporter (System Xc−), glutathione peroxidase 4 (GPX4) and glutathione (GSH) (System Xc−/GSH/GPX4 axis) plays a key role in preventing lipid peroxidation-mediated ferroptosis, because of which could be inhibited by blocking System Xc−/GSH/GPX4 axis. This review aims to present the current understanding of the mechanism of ferroptosis based on the System Xc−/GSH/GPX4 axis in the treatment of drug-resistant solid tumors.

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“…CuB also downregulates the expression of GPX4 [119]. Xie [122]. It has been indicated that brucine is a weakly alkaline compound isolated from the seeds of Strychnosnux-vomica, and induces the accumulation of H 2 O 2 , causing ferroptosis in glioma cells by upregulating ATF3 [123].…”

Section: Curculigoside Astragalus Polysaccharide and Astragalosidementioning

confidence: 99%

“…Gao et al have reported that Actinidia chinensis planch prevents gastric cancer by inducing apoptosis and ferroptosis in gastric cells [ 121 ]. Zhang et al showed that Bufotalin accelerates lipid peroxidation by inducing degradation of GPX4, and treats human non-small cell lung cancer (NSCLC) by targeting ferroptosis [ 122 ]. It has been indicated that brucine is a weakly alkaline compound isolated from the seeds of Strychnosnux-vomica, and induces the accumulation of H 2 O 2 , causing ferroptosis in glioma cells by upregulating ATF3 [ 123 ].…”

Section: The Main Tcms For Regulating Ferroptosismentioning

confidence: 99%

The Regulatory Effects of Traditional Chinese Medicine on Ferroptosis

Gao

Yin

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Traditional Chinese medicine (TCM) has significantly contributed to protecting human health and promoting the progress of world civilization. A total of 2,711 TCMs are included in the 2020 version of the Chinese Pharmacopoeia, which is an integral part of the world’s medical resources. Tu Youyou and her team discovered and purified artemisinin. And their contributions made the values and advantageous effects of TCM more and more recognized by the international community. There has been a lot of studies on TCM to treat diseases through antioxidant mechanisms, the reports on the new mechanisms beyond antioxidants of TCM has also increased year by year. Recently, many TCMs appear to have significant effects in regulating ferroptosis. Ferroptosis is an iron-dependent, non-apoptotic, regulated cell death characterized by intracellular lipid peroxide accumulation and oxidative membrane damage. Recently, accumulating studies have demonstrated that numerous organ injuries and pathophysiological process of many diseases are companied with ferroptosis, such as cancer, neurodegenerative disease, acute renal injury, arteriosclerosis, diabetes, and ischemia-reperfusion injury. This work mainly introduces dozens of TCMs that can regulate ferroptosis and their possible mechanisms and targets.

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Bufotalin induces ferroptosis in non-small cell lung cancer cells by facilitating the ubiquitination and degradation of GPX4

Cited by 81 publications

References 45 publications

The Ferroptosis Molecular Subtype Reveals Characteristics of the Tumor Microenvironment, Immunotherapeutic Response, and Prognosis in Gastric Cancer

The Ferroptosis Molecular Subtype Reveals Characteristics of the Tumor Microenvironment, Immunotherapeutic Response, and Prognosis in Gastric Cancer

System Xc−/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy

The Regulatory Effects of Traditional Chinese Medicine on Ferroptosis

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