ArticlePhytomedicine : international journal of phytotherapy and phytopharmacology2021
The isothiocyanate sulforaphane inhibits mTOR in an NRF2-independent manner.
Article in Phytomedicine : international journal of phytotherapy and phytopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Investigating the clinical efficacy, safety and molecular mechanism of sulforaphane in autism spectrum disorder: an integrated study combining meta-analysis, network pharmacology, and computational biology.BMC pharmacology & toxicology · 2025Pooled it
- Machine learning for discovering anticancer compounds from plants and elucidating their mechanisms.Journal of computer-aided molecular design · 2026Review
- Sulforaphane Decreases the Burden of AKT1-Expressing Pre-Neoplastic Cells in a Zebrafish Model of Glioblastoma Initiation.Nutrients · 2026Article
- Sulforaphane and Broccoli-Derived Preparations in Obesity and Obesity-Related Metabolic Dysfunction: Mechanistic Insights, Preclinical Evidence, and Clinical Perspectives.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Sulforaphane-Activated Functional Nucleic Acids for Cancer Therapy: Mechanisms, Delivery Strategies, and Nanomedicine Advances.International journal of molecular sciences · 2026Review
- Targeting the mTOR Pathway with Natural Products: A Potential Therapeutic Approach for Autism Spectrum Disorders.Current neuropharmacology · 2026Review
- Manganese modulates hepatocellular carcinoma cytotoxicity and doxorubicin sensitivity in a dose dependent manner.Frontiers in oncology · 2026Article
- Sulforaphane: a natural organosulfur having potential to modulate apoptosis and survival signalling in cancer.Discover oncology · 2025Review
- The dual role of mTOR signaling in lung development and adult lung diseases.Cell & bioscience · 2025Review
- The Effect ofAntioxidants (Basel, Switzerland) · 2024Article
- Multiple Mechanisms of Action of SulfodyneAntioxidants (Basel, Switzerland) · 2024Article
- Activation of Nrf2 at Critical Windows of Development Alters Tissue-Specific ProteinAntioxidants (Basel, Switzerland) · 2024Article
- Sulforaphane and ophthalmic diseases.Food science & nutrition · 2024Review
- Sulforaphane enhanced muscle growth by promoting lipid oxidation through modulating key signaling pathways.Bioscience reports · 2024Article
- Comparative Metabolomic Analysis ofInternational journal of molecular sciences · 2024Article
- Potential mechanisms of cancer prevention and treatment by sulforaphane, a natural small molecule compound of plant-derived.Molecular medicine (Cambridge, Mass.) · 2024Review
- mTOR Signaling Disruption and Its Association with the Development of Autism Spectrum Disorder.Molecules (Basel, Switzerland) · 2023Review
- The Multiple Sclerosis Modulatory Potential of Natural Multi-Targeting Antioxidants.Molecules (Basel, Switzerland) · 2022Review
- Synthesis and Anti-Inflammatory Activity of 2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-Derived NRF2 Activators.ChemistryOpen · 2022Article
- The effect of sulforaphane on perinatal hypoxic-ischemic brain injury in rats.Physiological research · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe isothiocyanate sulforaphane (SFN) has multiple protein targets in mammalian cells, affecting processes of fundamental importance for the maintenance of cellular homeostasis, among which are those regulated by the stress response transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) and the serine/threonine protein kinase mechanistic target of rapamycin (mTOR). Whereas the way by which SFN activates NRF2 is well established, the molecular mechanism(s) of how SFN inhibits mTOR is not understood. HYPOTHESIS/PURPOSE: The aim of this study was to investigate the mechanism(s) by which SFN inhibits mTOR STUDY DESIGN AND
methodsWe used the human osteosarcoma cell line U2OS and its CRISPR/Cas9-generated NRF2-knockout counterpart to test the requirement for NRF2 and the involvement of mTOR regulators in the SFN-mediated inhibition of mTOR.
resultsSFN inhibits mTOR in a concentration- and time-dependent manner, and this inhibition occurs in the presence or in the absence of NRF2. The phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B (PKB) is a positive regulator of mTOR, and treatment with SFN caused an increase in the phosphorylation of AKT at T308 and S473, two phosphorylation sites associated with AKT activation. Interestingly however, the levels of pS552 β-catenin, an AKT phosphorylation site, were decreased, suggesting that the catalytic activity of AKT was inhibited. In addition, SFN inhibited the activity of the cytoplasmic histone deacetylase 6 (HDAC6), the inhibition of which has been reported to promote the acetylation and decreases the kinase activity of AKT.
conclusionSFN inhibits HDAC6 and decreases the catalytic activity of AKT, and this partially explains the mechanism by which SFN inhibits mTOR.
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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.