ArticleCancers2020
Indoxylsulfate, a Metabolite of the Microbiome, Has Cytostatic Effects in Breast Cancer via Activation of AHR and PXR Receptors and Induction of Oxidative Stress.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
38 citing papers in PubMed, 53 citations in OpenAlex.
- Modulation of the response to immunotherapy in triple-negative breast cancer: the role of the microbiota and microbial metabolites in the tumor microenvironment.Gut microbes · 2026Review
- Molecular pathways linking the gut microbiome to antitumor immunity.Trends in microbiology · 2026Review
- Plasma proteome-metabolome signatures enable non-invasive early detection and lymph node risk stratification in breast cancer.Molecular cancer · 2026Article
- Indoxyl sulfate in the gut-kidney axis: from diet-microbiome interactions to renal injury and targeted therapies.Frontiers in nutrition · 2026Review
- Metagenomic analyses reveal E. coli-derived siderophores as potential signatures for breast cancer.Journal of translational medicine · 2025Article
- Bacterial metabolites: Effects on the development of breast cancer and therapeutic efficacy (Review).Oncology letters · 2025Review
- Insights into the gut microbiome-metabolite dynamics in breast cancer.Gut microbes reports · 2025Review
- Integrated analysis of microbiota and gut microbial metabolites in blood for breast cancer.mSystems · 2024Article
- Disentangling the molecular mystery of tumour-microbiota interactions: Microbial metabolites.Clinical and translational medicine · 2024Review
- Predictive analysis of breast cancer response to neoadjuvant chemotherapy through plasma metabolomics.Breast cancer research and treatment · 2024Article
- Microbial metabolites affect tumor progression, immunity and therapy prediction by reshaping the tumor microenvironment (Review).International journal of oncology · 2024Review
- Cytostatic Bacterial Metabolites Interfere with 5-Fluorouracil, Doxorubicin and Paclitaxel Efficiency in 4T1 Breast Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- The bacterial metabolite, lithocholic acid, has antineoplastic effects in pancreatic adenocarcinoma.Cell death discovery · 2024Article
- The microbiome: a link between obesity and breast cancer risk.Frontiers in microbiomes · 2024Review
- Anticarcinogenic effects of ursodeoxycholic acid in pancreatic adenocarcinoma cell models.Frontiers in cell and developmental biology · 2024Article
- Aryl hydrocarbon receptor: An emerging player in breast cancer pathogenesis and its potential as a drug target (Review).Molecular medicine reports · 2024Review
- The complex biology of aryl hydrocarbon receptor activation in cancer and beyond.Biochemical pharmacology · 2023Review
- Identification of Bacterial Metabolites Modulating Breast Cancer Cell Proliferation and Epithelial-Mesenchymal Transition.Molecules (Basel, Switzerland) · 2023Article
- Review
- Role of Gut Microbiota in Breast Cancer and Drug Resistance.Pathogens (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Changes to bacterial metabolite-elicited signaling, in oncobiosis associated with breast cancer, plays a role in facilitating the progression of the disease. We show that indoxyl-sulfate (IS), a tryptophan metabolite, has cytostatic properties in models of breast cancer. IS supplementation, in concentrations corresponding to the human serum reference range, suppressed tumor infiltration to the surrounding tissues and metastasis formation in a murine model of breast cancer. In cellular models, IS suppressed NRF2 and induced iNOS, leading to induction of oxidative and nitrosative stress, and, consequently, reduction of cell proliferation; enhanced oxidative and nitrosative stress are crucial in the subsequent cytostasis. IS also suppressed epithelial-to-mesenchymal transition vital for suppressing cellular movement and diapedesis. Furthermore, IS rendered cells hypometabolic, leading to a reduction in aldehyde-dehydrogenase positive cells. Pharmacological inhibition of the pregnane-X receptor using CH223191 and the aryl-hydrocarbon receptor using ketoconazole diminished the IS-elicited effects, suggesting that these receptors were the major receptors of IS in these models. Finally, we showed that increased expression of the human enzymes that form IS (Cyp2E1, Sult1A1, and Sult1A2) is associated with better survival in breast cancer, an effect that is lost in triple negative cases. Taken together, IS, similar to indolepropionic acid (another tryptophan metabolite), has cytostatic properties and higher expression of the metabolic machinery responsible for the formation of IS supports survival in breast cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.