ArticleCancer research2015
Naturally Occurring Isothiocyanates Exert Anticancer Effects by Inhibiting Deubiquitinating Enzymes.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 75 citations in OpenAlex.
- Isothiocyanates as Multi-Target Natural Compounds in Leukemia: Mechanisms, Selectivity, and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Natural Products Targeting BCR-ABL: A Plant-Based Approach to Chronic Myeloid Leukemia Treatment.Molecules (Basel, Switzerland) · 2025Review
- Integrating Phenotypic and Chemoproteomic Approaches to Identify Covalent Targets of Dietary Electrophiles in Platelets.ACS central science · 2024Article
- Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhIClBeilstein journal of organic chemistry · 2024Article
- Roles of USP9X in cellular functions and tumorigenesis (Review).Oncology letters · 2023Review
- Significant Benefits of Environmentally Friendly Hydrosols fromPlants (Basel, Switzerland) · 2023Article
- Phytochemicals as Immunomodulatory Agents in Melanoma.International journal of molecular sciences · 2023Review
- A new source of bacterial myrosinase isolated from endophytic Bacillus sp. NGB-B10, and its relevance in biological control activity.World journal of microbiology & biotechnology · 2022Article
- Hydrogen Sulfide Biology and Its Role in Cancer.Molecules (Basel, Switzerland) · 2022Review
- Assessment of Methodological Pipelines for the Determination of Isothiocyanates Derived from Natural Sources.Antioxidants (Basel, Switzerland) · 2022Review
- Bacterial-Assisted Extraction of Bioactive Compounds from Cauliflower.Plants (Basel, Switzerland) · 2022Article
- Natural compounds in the regulation of proteostatic pathways: An invincible artillery against stress, ageing, and diseases.Acta pharmaceutica Sinica. B · 2021Review
- Downregulated expression levels of USP46 promote the resistance of ovarian cancer to cisplatin and are regulated by PUM2.Molecular medicine reports · 2021Article
- A more sustainable isothiocyanate synthesis by amine catalyzed sulfurization of isocyanides with elemental sulfur.RSC advances · 2021Article
- Chemopreventive Effects of Dietary Isothiocyanates in Animal Models of Gastric Cancer and Synergistic Anticancer Effects With Cisplatin in Human Gastric Cancer Cells.Frontiers in pharmacology · 2021Article
- Repurposing old drugs as new inhibitors of the ubiquitin-proteasome pathway for cancer treatment.Seminars in cancer biology · 2021Review
- Deubiquitylase USP25 prevents degradation of BCR-ABL protein and ensures proliferation of Ph-positive leukemia cells.Oncogene · 2020Article
- Induction of Apoptosis by Gluconasturtiin-Isothiocyanate (GNST-ITC) in Human Hepatocarcinoma HepG2 Cells and Human Breast Adenocarcinoma MCF-7 Cells.Molecules (Basel, Switzerland) · 2020Article
- REX technologies for profiling and decoding the electrophile signaling axes mediated by Rosetta Stone proteins.Methods in enzymology · 2020Article
- Yeast screening system reveals the inhibitory mechanism of cancer cell proliferation by benzyl isothiocyanate through down-regulation of Mis12.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The anticancer properties of cruciferous vegetables are well known and attributed to an abundance of isothiocyanates such as benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC). While many potential targets of isothiocyanates have been proposed, a full understanding of the mechanisms underlying their anticancer activity has remained elusive. Here we report that BITC and PEITC effectively inhibit deubiquitinating enzymes (DUB), including the enzymes USP9x and UCH37, which are associated with tumorigenesis, at physiologically relevant concentrations and time scales. USP9x protects the antiapoptotic protein Mcl-1 from degradation, and cells dependent on Mcl-1 were especially sensitive to BITC and PEITC. These isothiocyanates increased Mcl-1 ubiquitination and either isothiocyanate treatment, or RNAi-mediated silencing of USP9x decreased Mcl-1 levels, consistent with the notion that USP9x is a primary target of isothiocyanate activity. These isothiocyanates also increased ubiquitination of the oncogenic fusion protein Bcr-Abl, resulting in degradation under low isothiocyanate concentrations and aggregation under high isothiocyanate concentrations. USP9x inhibition paralleled the decrease in Bcr-Abl levels induced by isothiocyanate treatment, and USP9x silencing was sufficient to decrease Bcr-Abl levels, further suggesting that Bcr-Abl is a USP9x substrate. Overall, our findings suggest that USP9x targeting is critical to the mechanism underpinning the well-established anticancer activity of isothiocyanate. We propose that the isothiocyanate-induced inhibition of DUBs may also explain how isothiocyanates affect inflammatory and DNA repair processes, thus offering a unifying theme in understanding the function and useful application of isothiocyanates to treat cancer as well as a variety of other pathologic conditions.
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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.