Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway

Kong, Zhaoyan; Liu, Rong; Cheng, Yuanrong

doi:10.1016/j.biopha.2018.11.030

Cited by 257 publications

(186 citation statements)

References 66 publications

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“…Ptgs2, also known as cyclooxygenase-2 (Cox-2), is the key enzyme in prostaglandin biosynthesis, and acts both as a peroxidase and as a dioxygenase [48,49]. We showed that Ptgs2 is involved in the process of ferroptosis because it was significantly upregulated after treatment with Rsl3 and erastin in mice [50][51][52]. These two small molecules were shown to be specific inducers of ferroptotic cell death and ideal probes to elucidate downstream regulators of ferroptosis [53][54][55].…”

Section: Discussionmentioning

confidence: 99%

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

et al. 2019

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Ferroptosis, a newly discovered form of iron-dependent regulated cell death, has been implicated in traumatic brain injury (TBI). MiR-212-5p has previously been reported to be downregulated in extracellular vesicles following TBI. To investigate whether miR-212-5p is involved in the ferroptotic neuronal death in TBI mice, we first examined the accumulation of malondialdehyde (MDA) and ferrous ion, and the expression of ferroptosis-related molecules at 6 h, 12 h, 24 h, 48 h and 72 h following controlled cortical impact (CCI) in mice. There was a significant upregulation in the expression of Gpx4 and Acsl4 at 6 h, Slc7a11 from 12 h to 72 h, and Nox2 and Sat1 from 6 h to 72 h post injury. Similarly, an upregulation in the expression of Gpx4 at 6 h, Nox2 from 6 h to 72 h, xCT from 12 h to 72 h, and Sat1 at 72 h after CCI was observed at the protein level. Interestingly, MDA and ferrous ion were increased whereas miR-212-5p was decreased in the CCI group compared to the sham group. Furthermore, we found that overexpression of miR-212-5p attenuated ferroptosis while downregulation of miR-212-5p promoted ferroptotic cell death partially by targeting prostaglandin-endoperoxide synthase-2 (Ptgs2) in HT-22 and Neuro-2a cell lines. In addition, administration of miR-212-5p in CCI mice significantly improved learning and spatial memory. Collectively, these findings indicate that miR-212-5p may protect against ferroptotic neuronal death in CCI mice partially by targeting Ptgs2.

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Section: Discussionmentioning

confidence: 99%

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

et al. 2019

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“…Oxidized PUFA-PLs create lipid hydroperoxides during ferroptosis by both enzymatic [the activation of the lipoxygenase-dependent enzymatic pathway involving ACSL4 (acyl-coA synthetase long-chain family member 4) and LPCAT3 (lysophosphatidylcholine acyltransferase 3)] and non-enzymatic (non-enzymatic free-radical chain reactions) pathways [58][59][60][61]. As a family of lipid peroxidizing enzymes, lipoxygenases participate in various types of cell death [62][63][64]. Several lipoxygenases are involved in promoting ferroptosis in human cells, such as ALOX5 (arachidonate 5lipoxygenase), ALOX12 (arachidonate 12-lipoxygenase, 12S type), ALOX12B (arachidonate 12-lipoxygenase, 12R type), ALOX15 (arachidonate 15-lipoxygenase), ALOX15B (arachidonate 15-lipoxygenase, type B) and ALOXE3 (arachidonate lipoxygenase 3) [58].…”

Section: Lipid Peroxidation-mediated Cytotoxicitymentioning

confidence: 99%

The epigenetic regulators and metabolic changes in ferroptosis-associated cancer progression

et al. 2020

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Ferroptosis, a novel form of regulated cell death, is different from other types of cell death in morphology, genetics and biochemistry. Increasing evidence indicates that ferroptosis has significant implications on cell death linked to cardiomyopathy, tumorigenesis, and cerebral hemorrhage to name a few. Here we summarize current literature on ferroptosis, including organelle dysfunction, signaling transduction pathways, metabolic reprogramming and epigenetic regulators in cancer progression. With regard to organelles, mitochondria-induced cysteine starvation, endoplasmic reticulum-related oxidative stress, lysosome dysfunction and golgi stress-related lipid peroxidation all contribute to induction of ferroptosis. Understanding the underlying mechanism in ferroptosis could provide insight into the treatment of various intractable diseases including cancers.

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“…Recently, ART‐induced ferritinophagy has also been reported to be involved in antifibrosis . In mouse hepatic stellate cells, ART triggers ferritinophagy accompanied byLC3 upregulation and ferritin heavy chain downregulation.…”

Section: Ferritinophagy Induction By Artesunatementioning

confidence: 99%

“…Recently, ART-induced ferritinophagy has also been reported to be involved in antifibrosis. 137 In mouse hepatic stellate cells, ART triggers ferritinophagy accompanied byLC3 upregulation and ferritin heavy chain downregulation. The depletion of ferritinophagy by the autophagy inhibitor CQ attenuates the antifibrosis function of ART, 137 providing new clues for further the pharmacological study of ART as a ferritinophagy modulator.…”

Section: Ferritinophagy Induction By Artesunatementioning

confidence: 99%

Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

Sun

Yan

Zou

et al. 2019

Medicinal Research Reviews

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Artemisinin and its derivatives, with their outstanding clinical efficacy and safety, represent the most effective and impactful antimalarial drugs. Apart from its antimalarial effect, artemisinin has also been shown to exhibit selective anticancer properties against multiple cancer types both in vitro and in vivo. Specifically, our previous studies highlighted the therapeutic effects of artemisinin on autophagy regulation. Autophagy is a well‐conserved degradative process that recycles cytoplasmic contents and organelles in lysosomes to maintain cellular homeostasis. The deregulation of autophagy is often observed in cancer cells, where it contributes to tumor adaptation to nutrient‐deficient tumor microenvironments. This review discusses recent advances in the anticancer properties of artemisinin and its derivatives via their regulation of autophagy, mitophagy, and ferritinophagy. In particular, we will discuss the mechanisms of artemisinin activation in cancer and novel findings regarding the role of artemisinin in regulating autophagy, which involves changes in multiple signaling pathways. More importantly, with increasing failure rates and the high cost of the development of novel anticancer drugs, the strategy of repurposing traditional therapeutic Chinese medicinal agents such as artemisinin to treat cancer provides a more attractive alternative. We believe that the topics covered here will be important in demonstrating the potential of artemisinin and its derivatives as safe and potent anticancer agents.

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Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway

Cited by 257 publications

References 66 publications

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2

The epigenetic regulators and metabolic changes in ferroptosis-associated cancer progression

Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

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