Myricetin inhibits interferon-γ-induced PD-L1 and IDO1 expression in lung cancer cells

He, Xinling; Lü, Qing; Wei, Shi; Yuan, Luo‐Wei; Huang, Mu‐Yang; Xu, Yan; Chen, Xiuping; Gu, Ling; Zhang, Le‐Le; Lu, Jin‐Jian

doi:10.1016/j.bcp.2022.114940

Cited by 27 publications

(17 citation statements)

References 72 publications

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“…In addition, flavonoids similar to puerarin, myricetin and flavonoids isolated from Sophora flavescens could suppress the expression of IDO1. [ 56 , 57 ]. So, we believed that the tryptophan-kynurenine metabolic pathway was delayed when puerarin entered the cell, which demonstrated that ferroptosis and inflammation were under control.…”

Section: Discussionmentioning

confidence: 99%

Puerarin Induces Molecular Details of Ferroptosis-Associated Anti-Inflammatory on RAW264.7 Macrophages

et al. 2022

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Puerarin is a natural flavonoid with significant anti-inflammatory effects. Recent studies have suggested that ferroptosis may involve puerarin countering inflammation. However, the mechanism of ferroptosis mediated by the anti-inflammatory process of puerarin has not been widely explored. Herein, puerarin at a concentration of 40 μM showed an anti-inflammatory effect on lipopolysaccharide (LPS)-induced macrophages RAW264.7. The analysis of network pharmacology indicated that 51 common targets were enriched in 136 pathways, and most of the pathways were associated with ferroptosis. Subsequently, the analysis of metabolomics obtained 61 differential metabolites that were enriched in 30 metabolic pathways. Furthermore, integrated network pharmacology and metabolomics revealed that puerarin exerted an excellent effect on anti-inflammatory in RAW264.7 via regulating ferroptosis-related arachidonic acid metabolism, tryptophan metabolism, and glutathione metabolism pathways, and metabolites such as 20-hydroxyeicosatetraenoic acid (20-HETE), serotonin, kynurenine, oxidized glutathione (GSSG), gamma-glutamylcysteine and cysteinylglycine were involved. In addition, the possible active binding sites of the potential targeted proteins such as acyl-CoA synthetase long-chain family member 4 (ACSL4), prostaglandin-endoperoxide synthase 2 (PTGS2), arachidonate 15-lipoxygenase (ALOX15) and glutathione peroxidase 4 (GPX4) with puerarin were further revealed by molecular docking. Thus, we suggested that ferroptosis mediated the anti-inflammatory effects of puerarin in macrophages RAW264.7 induced by LPS.

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Section: Discussionmentioning

confidence: 99%

Puerarin Induces Molecular Details of Ferroptosis-Associated Anti-Inflammatory on RAW264.7 Macrophages

et al. 2022

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“…[399][400][401] Moreover, the natural flavonoid myricetin was found to downregulate the levels of programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) and restore T-cell activity and antitumor immunity by inhibiting the IFN-γ-activated JAK-STAT-IRF1 axis in lung A549, breast MDA-MB-231 and colon HCT116 cancer cells. 402,403 Runtsch et al proposed that the natural metabolite itaconate and its derivatives inhibit M2 polarization by blocking JAK1-STAT6 pathway phosphorylation, providing a novel perspective on M2 macrophagedriven diseases. 404 As a new natural STAT3 inhibitor, XYA-2 was found to bind the SH2 domain of STAT3 and synergistically downregulate the levels of MYC and SLC39A10 in human gastric cancer cell lines and patient-derived xenograft (PDX) mouse models to perform its anticancer roles.…”

Section: Jak-stat Pathway and Treatmentmentioning

confidence: 99%

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Xue

Yao

et al. 2023

Sig Transduct Target Ther

129

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The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism of transmembrane signal transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, and other specific molecules activate JAK-STAT signaling to drive a series of physiological and pathological processes, including proliferation, metabolism, immune response, inflammation, and malignancy. Dysregulated JAK-STAT signaling and related genetic mutations are strongly associated with immune activation and cancer progression. Insights into the structures and functions of the JAK-STAT pathway have led to the development and approval of diverse drugs for the clinical treatment of diseases. Currently, drugs have been developed to mainly target the JAK-STAT pathway and are commonly divided into three subtypes: cytokine or receptor antibodies, JAK inhibitors, and STAT inhibitors. And novel agents also continue to be developed and tested in preclinical and clinical studies. The effectiveness and safety of each kind of drug also warrant further scientific trials before put into being clinical applications. Here, we review the current understanding of the fundamental composition and function of the JAK-STAT signaling pathway. We also discuss advancements in the understanding of JAK-STAT–related pathogenic mechanisms; targeted JAK-STAT therapies for various diseases, especially immune disorders, and cancers; newly developed JAK inhibitors; and current challenges and directions in the field.

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“…Additionally, myricetin restored the survival, proliferation, expression of CD69, and secretion of interleukin-2 in Jurkat-PD-1 T cells that had been suppressed by IFN-exposed lung cancer cells. Myricetin targeted and blocked the JAK-STAT-IRF1 axis, which was the mechanism by which IFN-upregulated PD-L1 and IDO1 at the transcriptional level [101]. The xenografts were created by transplanting A549 cells into immunodeficient mice.…”

Section: Lung Cancermentioning

confidence: 99%

Myricetin: A Significant Emphasis on Its Anticancer Potential via the Modulation of Inflammation and Signal Transduction Pathways

Rahmani

Almatroudi

Allemailem

et al. 2023

IJMS

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Cancer is a major public health concern worldwide and main burden of the healthcare system. Regrettably, most of the currently used cancer treatment approaches such as targeted therapy, chemotherapy, radiotherapy and surgery usually cause adverse complications including hair loss, bone density loss, vomiting, anemia and other complications. However, to overcome these limitations, there is an urgent need to search for the alternative anticancer drugs with better efficacy as well as less adverse complications. Based on the scientific evidences, it is proven that naturally occurring antioxidants present in medicinal plants or their bioactive compounds might constitute a good therapeutic approach in diseases management including cancer. In this regard, myricetin, a polyhydroxy flavonol found in a several types of plants and its role in diseases management as anti-oxidant, anti-inflammatory and hepato-protective has been documented. Moreover, its role in cancer prevention has been noticed through modulation of angiogenesis, inflammation, cell cycle arrest and induction of apoptosis. Furthermore, myricetin plays a significant role in cancer prevention through the inhibition of inflammatory markers such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2). Moreover, myricetin increases the chemotherapeutic potential of other anticancer drugs through modulation of cell signaling molecules activity. This review elaborates the information of myricetin role in cancer management through modulating of various cell-signaling molecules based on in vivo and in vitro studies. In addition, synergistic effect with currently used anticancer drugs and approaches to improve bioavailability are described. The evidences collected in this review will help different researchers to comprehend the information about its safety aspects, effective dose for different cancers and implication in clinical trials. Moreover, different challenges need to be focused on engineering different nanoformulations of myricetin to overcome the poor bioavailability, loading capacity, targeted delivery and premature release of this compound. Furthermore, some more derivatives of myricetin need to be synthesized to check their anticancer potential.

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Myricetin inhibits interferon-γ-induced PD-L1 and IDO1 expression in lung cancer cells

Cited by 27 publications

References 72 publications

Puerarin Induces Molecular Details of Ferroptosis-Associated Anti-Inflammatory on RAW264.7 Macrophages

Puerarin Induces Molecular Details of Ferroptosis-Associated Anti-Inflammatory on RAW264.7 Macrophages

Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Myricetin: A Significant Emphasis on Its Anticancer Potential via the Modulation of Inflammation and Signal Transduction Pathways

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