Our previous studies showed that phenethyl isothiocyanate (PEITC), a cruciferous vegetable constituent, inhibited the lung tumorigenesis induced by a potent tobacco-specific carcinogenic nitrosamine in animals. These results implicate dietary PEITC as a risk-reducing factor of lung cancers induced by smoking. To define the effect of dietary PEITC on human cancers, a method of measuring its uptake is needed. Since watercress is rich in gluconasturtiin, a glucosinolate precursor of PEITC, it was chosen to be the source of PEITC. Four individuals were asked to eat watercress as part of a breakfast meal, and 24-h urine samples were collected. A urinary metabolite was found, and its identity was confirmed as the N-acetylcysteine conjugate of PEITC by comparison with the synthetic standard using nuclear magnetic resonance and mass spectrometry. A dose-dependent excretion of this conjugate was observed. These results clearly showed that PEITC was released in the human body upon ingestion of watercress and suggest that the N-acetylcysteine conjugate of PEITC may be a useful marker for quantitating human exposure to this anticarcinogen as a tool for epidemiological investigations.
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Cell Rep Med
January 2025
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA. Electronic address:
Alpha-1 antitrypsin (AAT) deficiency (AATD) is a monogenic disease caused by misfolding of AAT variants resulting in gain-of-toxic aggregation in the liver and loss of monomer activity in the lung leading to chronic obstructive pulmonary disease (COPD). Using high-throughput screening, we discovered a bioactive natural product, phenethyl isothiocyanate (PEITC), highly enriched in cruciferous vegetables, including watercress and broccoli, which improves the level of monomer secretion and neutrophil elastase (NE) inhibitory activity of AAT-Z through the endoplasmic reticulum (ER) redox sensor protein disulfide isomerase (PDI) A4 (PDIA4). The intracellular polymer burden of AAT-Z can be managed by combination treatment of PEITC and an autophagy activator.
View Article and Find Full Text PDFMolecules
December 2024
Department of Surgery, School of Medicine, Virginia Commonwealth University, Richmond, VA 23284, USA.
Isothiocyanates (ITCs), found in edible plants such as cruciferous vegetables, are a group of reactive organo-sulfur phytochemicals produced by the hydrolysis of precursors known as glucosinolates. ITCs have been studied extensively both in vivo and in vitro to define their therapeutic potential for the treatment of chronic health conditions. Therapeutically, they have shown an intrinsic ability to inhibit oxidative and inflammatory phenotypes to support enhanced health.
View Article and Find Full Text PDFPhytother Res
December 2024
Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, Craiova, Romania.
Recent research has increasingly focused on phytochemicals as promising anticancer agents, with glucosinolates (GSLs) and their hydrolytic derivatives playing a central role. These sulfur-containing compounds, found in plants of the Brassicales order, are converted by myrosinase enzymes into biologically active products, primarily isothiocyanates (ITCs) and indoles, which exhibit significant anticancer properties. Indole-3-carbinol, diindolylmethane, sulforaphane (SFN), phenethyl isothiocyanate (PEITC), benzyl isothiocyanate, and allyl isothiocyanate have shown potent anticancer effects in animal models, particularly in breast, prostate, lung, melanoma, bladder, hepatoma, and gastrointestinal cancers.
View Article and Find Full Text PDFCancer Cell Int
December 2024
Department of Biology, University of Alabama at Birmingham, 3100 East Science Hall, 902 14th Street South, Birmingham, AL, 35294-1170, USA.
Background: Epigenetic phytochemicals are considered as an efficacious and safe alternative to synthetic drugs in drug discovery. In this regard, combinatorial interventions enable simultaneously targeting various neoplastic pathways to eradicate multiple tumorigenic clones. Therefore, we evaluated the effects of the epigenetic-modifying compounds phenethyl isothiocyanate (PEITC) and withaferin A (WA) alone and in combination on cancer hallmarks and miRNome profiles of breast cancer (BC) cells in addition to their impact on multiple epigenetic regulatory pathways.
View Article and Find Full Text PDFEur J Nutr
December 2024
Department of Medical Biology and Genetics, Faculty of Biology, University of Gdansk, Wita Stwosza 59, Gdansk, 80-308, Poland.
Purpose: Autophagy is a degradation process whose activation underlies beneficial effects of caloric restriction. Isothiocyanates (ITCs) induce autophagy in cancer cells, however, their impact on primary cells remains insufficiently explored, particularly in non-epithelial cells. The aim of this study was to investigate whether ITCs induce autophagy in primary (non-immortalized) mesenchymal cells and if so, to determine the molecular mechanism underlying its activation and consequences on cell functioning.
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