Resveratrol suppresses tumor progression via the regulation of indoleamine 2,3-dioxygenase

Noh, Kyung Tae; Chae, Seung Hoon; Chun, Sung Hak; Jung, In Duk; Kang, Hyo-Jin; Park, Yeong‐Min

doi:10.1016/j.bbrc.2012.12.093

Cited by 40 publications

(36 citation statements)

References 29 publications

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“…As noted above, IDO1 is the rate-limiting enzyme in the degradation of TRP, which exists in the placenta, epididymis, anterior chamber and gastrointestinal tract in addition to the liver [19, 20]. It was recently reported that IDO1 acts as an effector and an indicator of protective immune responses in patients with acute hepatitis B.…”

Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3-dioxygenase 1 deficiency attenuates CCl4-induced fibrosis through Th17 cells down-regulation and tryptophan 2,3-dioxygenase compensation

et al. 2017

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Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular rate-limiting enzyme in the metabolism of tryptophan along the kynurenine pathway, subsequently mediating the immune response; however, the role of IDO1 in liver fibrosis and cirrhosis is still unclear. In this study, we investigated the role of IDO1 in the development of hepatic fibrosis and cirrhosis. Patients with hepatitis B virus-induced cirrhosis and healthy volunteers were enrolled. For animals, carbon tetrachloride (CCl4) was used to establish liver fibrosis in wild-type and IDO1 knockout mice. Additionally, an IDO1 inhibitor (1-methyl-D-tryptophan) was administered to WT fibrosis mice. Liver lesions were positively correlated with serum IDO1 levels in both the clinical subjects and hepatic fibrosis mice. A positive correlation between serum IDO1 levels and liver stiffness values was found in the cirrhosis patients. Notably, IDO1 knockout mice were protected from CCl4-induced liver fibrosis, as reflected by unchanged serum alanine transaminase and aspartate transaminase levels and lower collagen deposition, α-smooth muscle actin expression and apoptotic cell death rates. On the other hand, tryptophan 2,3-dioxygenase (TDO), another systemic tryptophan metabolism enzyme, exhibited a compensatory increase as a result of IDO1 deficiency. Moreover, hepatic interleukin-17a, a characteristic cytokine of T helper 17 (Th17) cells, and downstream cytokines’ mRNA levels showed lower expression in the IDO1–/– model mice. IDO1 appears to be a potential hallmark of liver lesions, and its deficiency protects mice from CCl4-induced fibrosis mediated by Th17 cells down-regulation and TDO compensation.

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Section: Discussionmentioning

confidence: 99%

Indoleamine 2,3-dioxygenase 1 deficiency attenuates CCl4-induced fibrosis through Th17 cells down-regulation and tryptophan 2,3-dioxygenase compensation

et al. 2017

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“…Another mechanism by which resveratrol impairs the immunosuppressive TME is by inhibiting IFN‐γ–induced IDO expression and activity in bone marrow‐derived DCs. Accordingly, the potential of resveratrol to reduce EG7 thymoma xenograft tumor growth is IDO‐dependent and is associated with the regulation of CTL polarization and enhanced cytolytic activity . Conversely, resveratrol upregulates MICA/MICB mRNA and protein expression levels in breast cancer cells, which, in turn, enhances breast cancer cytolysis by NK cells in vitro and in vivo.…”

Section: Natural Compounds Possessing Epigenetic Properties That Stimmentioning

confidence: 99%

“…Accordingly, the potential of resveratrol to reduce EG7 thymoma xenograft tumor growth is IDO-dependent and is associated with the regulation of CTL polarization and enhanced cytolytic activity. 90 Conversely, resveratrol upregulates MICA/ MICB mRNA and protein expression levels in breast cancer cells, which, in turn, enhances breast cancer cytolysis by NK cells in vitro and in vivo. In that study, the authors also demonstrated that resveratrol downregulates c-Myc-dependent miR-17 expression, which, if untreated, represses MICA/MICB expression.…”

Section: Curcuminmentioning

confidence: 99%

Anticancer potential of naturally occurring immunoepigenetic modulators: A promising avenue?

Schnekenburger

Dicato

Diederich

2019

Cancer

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The immune system represents the major primary defense line against carcinogenesis and acts by identifying and eradicating nascent transformed cells. A growing body of evidence is indicating that aberrant epigenetic reprogramming plays a key role in tumor immune escape through: 1) impaired efficient recognition of neoplastic cells by the immune system, resulting from a downregulation or loss of the expression of tumor‐associated antigens, human leukocyte antigens, antigen processing and presenting machinery, and costimulatory molecule genes; 2) aberrant expression of immune checkpoint proteins and their ligands; and 3) modification of cytokine profiles and tumor‐associated immune cell populations toward an immunosuppressive state in the tumor microenvironment. Consistent with the inherent reversibility of epigenetic alterations, epigenetic drugs, including DNA methyltransferase and histone deacetylase inhibitors, have the unique potential to favorably modify the tumor microenvironment, restore tumor recognition and stimulate an antitumor immune response. The objective of this review is to highlight selected, naturally occurring epigenetic modulators, namely, butyrate, curcumin, (−)‐epigallocatechin‐3‐gallate, resveratrol, romidepsin, and trichostatin A, with a special focus on their antitumor immune properties.

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“…These IDO-reactive T cells are able to recognize and kill tumor cells as well as IDO-expressing DCs, that is, one of the main immunesuppressive cell populations (Sørensen et al 2011 ). Inhibition of the expression and activity of IFN-gamma-induced IDO in bone marrow-derived dendritic cells (BMDCs) through the suppression of the activity of Janus kinase/signal transducers and activators of transcription (JAK/STAT) and protein kinase C causes antitumor activity by regulating CD8+ T-cell polarization and CTLs activity (Noh et al 2013 ).…”

Section: Immune Escape Mechanism In Cancermentioning

confidence: 99%

Evaluation of Tryptophan Metabolism in Chronic Immune Activation

Engin

2015

Tryptophan Metabolism: Implications for Biological Processes, Health and Disease

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Chronic immune activation is encountered in different pathologies including granulomatous and functional bowel diseases, cancer, aging, atherosclerosis, and obesity. Persistence of chronic infl ammatory stimuli over time creates a biologic background for immunosenescence and favors neopterin formation with the enhanced tryptophan (Trp) degradation in diseases concomitant with cellular immune activation. Trp degradation leads to the generation of several neuroactive compounds by three distinct pathways.Indoleamine 2,3-dioxygenase (IDO) induction leads to many complex changes within the affected cells resulting in immunosuppression through breakdown of Trp. Thus, neopterin concentrations as well as IDO expression signifi cantly increase in infl ammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease.However, irritable bowel syndrome (IBS) is linked with abnormal serotonin functioning and immune activation. In this case, enteric serotonin (5-HT) signaling may be defective and inactivated by the serotonin-selective reuptake transporter (SERT) in the enterocytes. A positive correlation is evident between IBS severity and kynurenine (Kyn) to Trp ratio which is signifi cantly correlated with the rise of interferon (IFN)-gamma.The dual host-protective and tumor-promoting actions of immunity are referred to as cancer immunoediting. IDO-reactive T cells are able to recognize and kill tumor cells as well as IDO-expressing dendritic cells (DCs). IDO activation leads to immunosuppression through breakdown of Trp in the tumor microenvironment and tumor-draining lymph nodes. C-C chemokine receptor type 4 (CCR4)+ forkhead boxp3(Foxp3)+ regulatory T (Treg) cells create a favorable environment for tumor escape from host immune responses. Thus, Foxp3+/IDO+ tumors are associated with more advanced disease.Age-related changes in the immune system are known as immunosenescence. A causal relationship is evident between the Trp metabolism and immune defi ciency in elderly. Eventually, the reduced serum Trp concentrations and increased Kyn levels indicate increased chronic low-grade infl ammation in elderly. In this case,

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Resveratrol suppresses tumor progression via the regulation of indoleamine 2,3-dioxygenase

Cited by 40 publications

References 29 publications

Indoleamine 2,3-dioxygenase 1 deficiency attenuates CCl4-induced fibrosis through Th17 cells down-regulation and tryptophan 2,3-dioxygenase compensation

Indoleamine 2,3-dioxygenase 1 deficiency attenuates CCl4-induced fibrosis through Th17 cells down-regulation and tryptophan 2,3-dioxygenase compensation

Anticancer potential of naturally occurring immunoepigenetic modulators: A promising avenue?

Evaluation of Tryptophan Metabolism in Chronic Immune Activation

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