Ponicidin suppresses pancreatic cancer growth by inducing ferroptosis: Insight gained by mass spectrometry-based metabolomics

Cui, Weiqi; Zhang, Junwei; Wu, Deqiao; Zhang, Jingxian; Zhou, Hui; Rong, Ying; Liu, Fanglin; Wei, Bo; Xu, Xia

doi:10.1016/j.phymed.2022.153943

Cited by 18 publications

(10 citation statements)

References 33 publications

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“…The resulting data were modeled using SIMCA software and the relationship between groups was analyzed by orthogonal partial least squares discriminant analysis (OPLS-DA). 27,28 At the same time, the results of Fit Plot and Permutations Plot were used to analyze the quality of the model and avoid overfitting.…”

Section: Analysis Of Metabolomics Resultsmentioning

confidence: 99%

“…Noteworthy, the inhibition of glutathione biosynthesis significantly reduced the levels of strong antioxidants GSH and GPX4, and the abnormal upregulation of polyunsaturated fatty acid biosynthetic pathways significantly exacerbated cellular oxidative stress, which further promoted the occurrence of ferroptosis. 20,22,27 Importantly, liver possesses the endogenous antioxidants or anti-oxidative stress enzymes, including glutathione and GPX4. 46,47 Thereby, reducing the accumulation of lipid peroxides and inhibiting the release of proinflammatory factors in the liver would exert hepatoprotective effects.…”

Section: Discussionmentioning

confidence: 99%

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Hepatoprotective effect of Artemisia Argyi essential oil on bisphenol A‐induced hepatotoxicity via inhibition of ferroptosis in mice

Cui

Zhou

Zhang

et al. 2023

Environmental Toxicology

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The environmental pollutant bisphenol A (BPA), used in the manufacture of plastic packaging materials for various diets, is widely distributed in the environment and causes severe hepatotoxicity by inducing oxidative stress. Artemisia argyi essential oil (AAEO), a volatile oil component isolated from Artemisia argyi H.Lév. & Vaniot, has pharmacological effects, especially for hepatoprotective actions. However, the potential effect of AAEO in BPA induced hepatotoxicity has not been characterized. First, we analyzed the chemical composition in AAEO by gas chromatography–mass spectrometry. Herein, we investigated the effect of AAEO on hepatic metabolic changes in mice exposed to BPA. Results showed that compared with the BPA group, AAEO could reduce the level of liver function enzymes in BPA mice serum, and ameliorate hepatic lesions and fibrosis. Additionally, 20 differential metabolites screened by metabolomics were mainly involved in the reprogramming of glutathione metabolism, purine metabolism, and polyunsaturated fatty acid synthesis. Moreover, AAEO could reduce hepatic ferroptosis induced by BPA, as demonstrated by reducing xanthine oxidase activity, up‐regulating the activities of glutathione peroxidase 4 (GPX4), superoxide dismutase, and catalase and the expression of SLC7A11 to promote the glutathione synthetic, while inhibiting transferrin receptor 1 (TFR1) expression to reduce the accumulation of Fe2+ in cells. Therefore, our study identified AAEO as a hepatic protectant against BPA‐induced hepatotoxicity by reversing the occurrence of ferroptosis.

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Section: Analysis Of Metabolomics Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hepatoprotective effect of Artemisia Argyi essential oil on bisphenol A‐induced hepatotoxicity via inhibition of ferroptosis in mice

Cui

Zhou

Zhang

et al. 2023

Environmental Toxicology

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“…Chrysin enhances pancreatic cancer sensitivity to gemcitabine by inducing autophagy-dependent ferroptosis via the targeting of human carbonyl reductase 1 [122]. Ponicidin suppresses pancreatic cancer growth by inducing ferroptosis [123], while piperlongumine induces ferroptosis in human pancreatic cancer cells by suppressing the gamma-glutamyl cycle and regulating the metabolism of PUFAs [124].…”

Section: Pancreatic Cancermentioning

confidence: 99%

Ferroptosis and Its Role in Chronic Diseases

Liu

Zhu

et al. 2022

Cells

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Ferroptosis, which has been widely associated with many diseases, is an iron-dependent regulated cell death characterized by intracellular lipid peroxide accumulation. It exhibits morphological, biochemical, and genetic characteristics that are unique in comparison to other types of cell death. The course of ferroptosis can be accurately regulated by the metabolism of iron, lipids, amino acids, and various signal pathways. In this review, we summarize the basic characteristics of ferroptosis, its regulation, as well as the relationship between ferroptosis and chronic diseases such as cancer, nervous system diseases, metabolic diseases, and inflammatory bowel diseases. Finally, we describe the regulatory effects of food-borne active ingredients on ferroptosis.

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“…Ponicidin also exhibited antibacterial properties, anti-inflammatory as well as anti-viral properties. 21 Cui et al 22 found that the ponicidin suppressed the growth and induced ferroptosis in pancreatic cancer. However, the ameliorative roles of ponicidin against MI are not been scientifically discussed yet.…”

Section: Introductionmentioning

confidence: 99%

Ameliorative Effects of Ponicidin Against the Isoproterenol-induced Acute Myocardial Infarction in Rats

Zhang¹,

Seshadri

Jiang³

2023

Pharmacognosy Magazine

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Background Cardiovascular disease (CVD) is a group of heart disorders, which is a major cause of noncommunicable disease-related mortalities worldwide. Myocardial infarction (MI) is an acute disorder due to the poor supply of oxygen and blood to the myocardium. MI is the foremost form of CVD, which is the primary cause of mortality worldwide. Objectives Here, we intended to discover the ameliorative properties of the ponicidin against the isoproterenol (ISO)-stimulated MI in rats. Methodology About 85 mg/kg of ISO was administered to the rats to trigger the MI and then treated with 25 and 50 mg/kg of ponicidin. The body weight and heart weight of all rats were determined. The total protein, c-reactive protein (CRP), and uric acid levels were examined. The activities of cardiac function markers such as creatine kinase (CK), ALT, AST, and gamma-glutamyl transferase (GGT) were examined. The antioxidants such as glutathione (GSH), GST, and GPx were examined by the previous methods. The status of Na+/K+, Mg2+, and Ca2+ ATPase activities was assessed using kits. The status of Na+, K+, and Ca2+ ions and inflammatory makers such as TNF-α and IL-6 were investigated using respective kits. The histopathological analysis was performed on the heart tissues to detect the histological changes. Results The results revealed that ponicidin increased body weight and decreased heart weight in MI rats. The status of CRP and uric acid was decreased and total protein was augmented in the ponicidin-treated MI rats. The AST, ALT, CK, and GGT activities were appreciably decreased in serum and elevated in the cardiac tissues of the ponicidin-administered MI rats. Furthermore, the ponicidin improved the antioxidant levels, decreased the TNF-α and IL-6, and regulated the Na+, K+, and Ca2+ ion transports in the MI rats. The activities of Na+/K+, Mg2+, and Ca2+ ATPase enzymes were remarkably increased in the heart tissues by the ponicidin-treated MI rats. Ponicidin treatment also ameliorated the ISO-stimulated histological alterations in the heart tissue of the MI rats. Conclusion Ponicidin treatment appreciably improved the antioxidants, Na+/K+, Mg2+, and Ca2+ ATPase enzyme activities, decreased the inflammatory markers, and regulated the cardiac marker enzyme activities in the MI rats. Hence, it can be a talented therapeutic candidate in the future to treat MI.

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Ponicidin suppresses pancreatic cancer growth by inducing ferroptosis: Insight gained by mass spectrometry-based metabolomics

Cited by 18 publications

References 33 publications

Hepatoprotective effect of Artemisia Argyi essential oil on bisphenol A‐induced hepatotoxicity via inhibition of ferroptosis in mice

Hepatoprotective effect of Artemisia Argyi essential oil on bisphenol A‐induced hepatotoxicity via inhibition of ferroptosis in mice

Ferroptosis and Its Role in Chronic Diseases

Ameliorative Effects of Ponicidin Against the Isoproterenol-induced Acute Myocardial Infarction in Rats

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