SULFORAPHANE ACUTELY ACTIVATES MULTIPLE STARVATION RESPONSE PATHWAYS
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ABSTRACT:
PROVIDER: PRJNA1150243 | ENA |
REPOSITORIES: ENA
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Project description:Sulforaphane (SFN) is an isothiocyanate present in cruciferous vegetables that ameliorates various disease models in rodents (e.g., cancer, diabetes, seizures) that are likewise mitigated by dietary restriction leading us to test the hypothesis that this compound elicits cellular responses consistent with being a fasting mimetic. Using untransformed human retinal pigment epithelial (RPE-1) cells, we report that SFN impacted multiple nutrient-sensing pathways consistent with a fasting state. SFN treatment (i) increased mitochondrial resistance to oxidative stress, (ii) acutely suppressed markers of mTORC1/2 activity via inhibition of insulin signaling, (iii) upregulated autophagy and further amplified autophagic flux induced by rapamycin or nutrient deprivation while concomitantly promoting lysosomal and mitochondrial biogenesis, (iv) acutely decreased glucose uptake and lactate secretion followed by an adaptive rebound that coincided with suppressed protein levels of thioredoxin-interacting protein (TXNIP) due to early transcriptional down-regulation. This early suppression of TXNIP mRNA expression could be overcome with exogenous glucosamine consistent with SFN inhibiting glutamine F6P amidotransferase (GFAT), the rate limiting enzyme of the hexosamine biosynthetic pathway. SFN also altered multiple glycolytic and tricarboxylic acid (TCA) cycle intermediates while reducing the inhibitory phosphorylation on pyruvate dehydrogenase, indicative of an adaptive cellular starvation response directing pyruvate into acetyl coenzyme A for uptake by the TCA cycle. RNA-seq of cells treated for 4hrs with SFN confirmed the activation of signature starvation-responsive transcriptional programs. Concomitant with stabilizing and activating the transcription factor NF-E2-related factor 2, we posit that the fasting-mimetic properties of SFN underlie both the therapeutic efficacy and potential toxicity of this phytochemical.
2024-11-28 | GSE275316 | GEO
Project description:Sulforaphane and sulforaphene are isothiocyanate compounds derived from cruciferous vegetables that have demonstrated antiproliferative properties against colon cancer. However, the underlying mechanism of action of these two compounds is yet to be elucidated. The present study aimed to study the effects of sulforaphane and sulforaphene on colon cancer by next-generation sequencing (NGS).
2021-05-15 | GSE174444 | GEO
Project description:Protective roles of Nrf2, a key transcription factor for antioxidant and defense genes, have been determined in oxidative lung injury, and health benefits of Nrf2 agonists including sulforaphane have been demonstrated. The current study was designed to investigate the effect of sulforaphane on model acute lung injury and sulforaphane-mediated transcriptome changes in mouse lungs. Adult mice genetically deficient in Nrf2 (Nrf2-/-) and wild-type controls (Nrf2+/+, ICR) received oral sulforaphane (9 mmol/daily) or vehicle before (-5, -3, -1 days) hyperoxia or air exposure (3 days), and lung injury and gene expression changes were assessed. Sulforaphane significantly reduced hyperoxia-induced airway injury, inflammation, and mucus hypersecretion in Nrf2+/+ mice while relatively marginal treatment effect was found in Nrf2-/- mice. Sulforaphane significantly altered expression of lung genes associated with oxidative phosphorylation and mitochondrial dysfunction (Atp2a2, Cox7a1, Ndufa1) basally and cell function/cycle and protein metabolism (Actr1a, Wasf2, Ccne1, Gtpbp4) after hyperoxia in Nrf2+/+ mice. Nrf2-dependently modulated lung genes by sulforaphane and hyperoxia were associated with tissue development and hereditary disorders (Slc25a3, Pccb, Psmc3ip). Results demonstrate preventive roles of sulforaphane against oxidant lung injury in mice, and reveal potential downstream mechanisms. Our observations also suggest Nrf2-independent mechanisms of sulforaphane in prevention of acute lung injury.
2015-06-01 | GSE58654 | GEO
Project description:Sulforaphane is a naturally occurring, potent antioxidant and anti-inflammatory compound, found in cruciferous plants such as broccoli. Recently there have been a large number of clinical trials assessing broccoli sprout extracts as sulforaphane-based therapies for conditions including fibrosis, cancer and preeclampsia. As sulforaphane is orally administered, there is also the potential for impact on the gut microbiome. Here, we have determined the effect of sulforaphane on the growth of 43 common human gastrointestinal bacterial commensals and pathogens, which represented the four main phyla found in the human gastrointestinal microbiome. The pathogenic Escherichia coli strain ECE2348/69 showed the most significant increases in growth in the presence of sulforaphane compared to control conditions. Proteomic analysis of this isolate showed that sulforaphane increased anaerobic respiration, whilst metabolomic profiling identified differentially produced metabolites involved in amino acid biosynthesis and known to decrease inflammation in human cells. Therefore, sulforaphane can increase growth of specific gastrointestinal bacterial isolates, correlating with increased production of anti-inflammatory metabolites, that may provide a novel mechanism for modulating inflammatory states in patients.
2023-07-19 | PXD040621 | Pride
Project description:The effect of sulforaphane on the expression of microRNAs in colorectal adenocarcinoma Caco-2 cells and non-cancerous colorectal CCD-841 cells was investigated, in order to help ascertain the roles of microRNAs in the anti-cancer effects of sulforaphane.
2020-06-30 | GSE89363 | GEO
Project description:H460 cells treated with vehicle or sulforaphane (SFN) for 48 hours were used to acquire expression profiles of a total of 1891 unique miRNAs. We aimed at identifying the differentially expressed miRNAs between cells treated or untreated with SFN.
2018-05-05 | GSE81143 | GEO
Project description:Recent pre-clinical data provide strong evidence that short-term starvation before the administration of cytostatic drugs for the chemotherapy of solid tumors leads to significantly higher efficacy and lower toxicity levels. However, these findings have so far not been validated in patients. The aim of this trial is to provide first clinical evidence regarding the impact of pre-chemotherapeutic short-term starvation on response to therapy (primary endpoint). Additionally, progression-free survival, adverse events, and overall survival will be monitored (secondary endpoints). In perspective, short-term starvation before chemotherapy could represent a simple and secure way to improve both efficacy and tolerance of chemotherapies at low cost.
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Project description:Effect of sulforaphane (SF) on human colon caco-2 cells after 24h treatment
2005-07-01 | E-MEXP-170 | biostudies-arrayexpress
Project description:Blood samples were collected from healthy volunteers, PBMC were collected using standard ficoll centrifugation. RNA was collected from untreated and PBMC treated with 15 µM L-sulforaphane for 24 hours. Libraries were prepared for mRNA-Seq.
2022-01-09 | GSE160353 | GEO