2020
DOI: 10.3390/cancers12092411
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Abstract: Oncobiotic transformation of the gut microbiome may contribute to the risk of breast cancer. Recent studies have provided evidence that the microbiome secretes cytostatic metabolites that inhibit the proliferation, movement, and metastasis formation of cancer cells. In this study, we show that indolepropionic acid (IPA), a bacterial tryptophan metabolite, has cytostatic properties. IPA selectively targeted breast cancer cells, but it had no effects on non-transformed, primary fibroblasts. In cell-based and ani… Show more

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Cited by 72 publications
(84 citation statements)
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“…This could indicate that these cell types are more sensitive to IPA compared to cardiomyocytes. A further explanation for this finding could be activation of pregnane X receptor (PXR) by IPA, as previously described (31,45). PXR is a xenobiotic receptor, which is predominantly expressed in gastrointestinal and liver tissue, but has also been described in HUVEC before (94,95).…”
Section: Discussionmentioning
confidence: 75%
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“…This could indicate that these cell types are more sensitive to IPA compared to cardiomyocytes. A further explanation for this finding could be activation of pregnane X receptor (PXR) by IPA, as previously described (31,45). PXR is a xenobiotic receptor, which is predominantly expressed in gastrointestinal and liver tissue, but has also been described in HUVEC before (94,95).…”
Section: Discussionmentioning
confidence: 75%
“…Effects of IPA in other cell types have been described. The inhibitory effect of IPA on cell proliferation was, for example, observed in breast cancer cells, but mitochondrial function was not investigated ( 45 ). Besides an inhibition of maximal respiration, we observed in both cell types that also basal respiration was significantly reduced.…”
Section: Discussionmentioning
confidence: 99%
“…Microbiome-neoplastic cell interactions are multi-pronged (Miko et al 2016 ; Miko et al 2019 ; Zitvogel et al 2017 ; Kovacs et al 2020 ; Finlay et al 2020 ) and can impact on multiple cancer hallmarks (for cancer hallmarks, see the seminal papers of Hanahan and Weinberg (Hanahan and Weinberg 2011 , 2000 )). Microbiome-related effects stem from basic cellular functions, such as changes to redox homeostasis (Kovács et al 2019 ; Smolková et al 2020 ; Sári et al 2020a , b ) or changes to cellular metabolism (Sári et al 2020a , b ; Miko et al 2018 ; Kovács et al 2019 ), via altered gene expression patterns. These primary changes then modulate larger scale events, namely, epithelial-to-mesenchymal transition (Sári et al 2020b ; Miko et al 2018 ; Kovács et al 2019 ; Buchta Rosean et al 2019 ; Ingman 2019 ; Vergara et al 2019 ), cancer cellular movement, invasion, diapedesis and metastasis formation (Kovács et al 2019 ; Sári et al 2020a , b , 2020 ; Miko et al 2018 ; Kovács et al 2019 ), angiogenesis (Miko et al 2018 ), the modulation of antitumor immunity (Sári et al 2020a ; Miko et al 2018 ; Vergara et al 2019 ; Sipe et al 2020 ; Osman and Luke 2019 ; Zitvogel et al 2016 ; Routy et al 2018a , 2018b ; Gopalakrishnan et al 2018 ; Elkrief et al 2019 ; Derosa et al 2020 ; Hall and Versalovic 2018 ; Viaud et al 2014 ), and tumor-promoting inflammation (Kiss et al 2020 ; Yu 2018 ).…”
Section: Interactions Between the Oncobiome And Cancermentioning
confidence: 99%
“…In this case, the dysbiotic microbiome drives local inflammation upon pathological colonization, such as in ovarian carcinoma (Wang et al 2020 ) or pancreas adenocarcinoma (Kiss et al 2020 ). On the contrary, low oxidative stress, induced by bacterial metabolites, can exert cytostatic (but not cytotoxic) properties, as in the downregulation of NRF2 in breast cancer (Kovács et al 2019 ; Sári et al 2020a , b ).…”
Section: Interactions Between the Oncobiome And Cancermentioning
confidence: 99%
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