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Gastrointestinal cancers remain a global health burden, demanding more effective prevention and treatments. Phenethyl isothiocyanate (PEITC), a compound derived from cruciferous vegetables, stands out as a promising nutraceutical agent due to its chemopreventive and therapeutic properties. However, its therapeutic translation remains limited mainly due to its poor water solubility and rapid metabolism. Herein, we encapsulated PEITC into biocompatible chitosan-based microparticles with an extra virgin olive oil core to improve its bioavailability and stability. Pure PEITC's biocompatibility and microencapsulated PEITC's stability and antibacterial activity were evaluated. The antibacterial activity analysis showed microencapsulated PEITC as a promising antibacterial agent against gastrointestinal pathogenic bacteria (two Gram-positive and two Gram-negative). The impact of both pure and microencapsulated PEITC was assessed on gastrointestinal cancer cells (MKN45 gastric cancer and SW48 colon cancer cell lines). PEITC exhibited threshold or hormetic dose-dependent toxicity in colon fibroblasts and decreased gastric cancer cells' migration capacity, enhanced upon encapsulation into microparticles. In addition, microencapsulated PEITC induced downregulation of phosphorylated AKT, FAK, and ERK1/2 proteins, disrupting motility signaling pathways and tubulin expression. These findings suggest that the delivery of PEITC via chitosan-based microparticles holds promise as a nutraceutical delivery strategy against gastrointestinal disorders that predispose to cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Phenethyl isothiocyanate (PEITC) is an aromatic isothiocyanate present in cruciferous vegetables. Several studies have shown that isothiocyanates regulate various intracellular signaling pathways, and thereby show anti-inflammatory and detoxifying activities. However, little is known about the effects of PEITC on glucose metabolism. In this study, we examined whether PEITC promotes glucose utilization in mouse skeletal muscle cells, C2C12 myotubes. PEITC induced glucose uptake, glucose transporter 4 (Glut4) translocation to the plasma membrane, and activation of Akt and ERK in C2C12 cells. Inhibition of Akt suppressed PEITC-induced Glut4 translocation and glucose uptake, whereas ERK inhibition did not. Furthermore, PEITC increased phosphorylation of ErbB2 and ErbB3. Treatment with a pan-ErbB inhibitor reduced Akt activation and the subsequent glucose uptake induced by PEITC. These results indicate that PEITC promotes glucose utilization through the ErbB/Akt pathway in C2C12 myotubes. PEITC may therefore serve as a dietary constituent with beneficial effects on the carbohydrate metabolism. Abbreviations: PEITC: phenethyl isothiocyanate; Glut4: glucose transporter 4; PI3K: phosphatidylinositide 3-kinase; Nrf2: erythroid−2-related factor; ARE: antioxidant response element; HO−1: heme oxygenase−1; NRG: neuregulin Phenethyl isothiocyanate (PEITC), a dietary isothiocyanate in cruciferous vegetables, induces glucose uptake in C2C12 myotubes through activation of the ErbB/Akt pathway. [ABSTRACT FROM AUTHOR]

Obesity is associated with systemic oxidative stress and leads to insulin resistance. Phenethyl isothiocyanate (PEITC), a natural dietary isothiocyanate, has been shown to have beneficial effects in improving cellular defense activities against oxidative stress through activation of nuclear factor erythroid-2 related factor 2 (Nrf2) pathway. However, little evidence exists if the antioxidative activity has beneficial effects on glucose metabolism. Here, we tested the preventive potential of PEITC for impaired insulin-induced glucose uptake by oxidative stress in 3T3-L1 adipocytes. Treatment with PEITC increased the expression of antioxidative enzymes regulated by Nrf2 such as γ-glutamylcysteine-synthetase, heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1 and glutathione S-transferase, and reduced oxidative stress induced by H2O2. Furthermore, PEITC restored impaired insulin-stimulated glucose uptake, translocation of glucose transporter 4 and insulin signaling by H2O2. These results indicate that PEITC protected insulin-regulated glucose metabolism impaired by oxidative stress through the antioxidative activity in 3T3-L1 adipocytes. Phenethyl isothiocyanate (PEITC) protects from insulin resistance induced by oxidative stress in 3T3-L1 adipocytes. [ABSTRACT FROM AUTHOR]

Abstract: The potentials of sulforaphane and phenethyl isothiocyanate as functional food ingredients against hematological malignancies were evaluated on the intracellular targets of these antiangiogenic compounds in CEM/C2 T leukemia cells. CEM/C2 cells were seeded and incubated with various concentrations of sulforaphane or phenethyl isothiocyanate for 24 or 48h. Sulforaphane at 0–30μmol/L dose-dependently suppressed CEM/C2 cell growth and proliferation and caused cell death by apoptosis with down-regulation of bcl-2 and increased release of cytochrome c within 48h. Phenethyl isothiocyanate at 0–15μmol/L dose-dependently inhibited CEM/C2 cell viability within 48h and caused cell death by apoptosis with down-regulation of bcl-2 and increased expression of cytochrome c. CEM/C2 cell death was accompanied by inhibition of IκB phosphorylation and degradation and nuclear translocation of p65-nuclear factor kappaB (NF-κB) by sulforaphane as well as phenethyl isothiocyanate. CEM/C2 cell viability and proliferation can be inhibited by functional food ingredient inhibitors of the NF-κB pathway. [Copyright &y& Elsevier]

Background: Phenethyl isothiocyanate (PEITC) is a glucosinolate derived from cruciferous vegetables and is a cancer-chemopreventive reagent. Cancer stem cells (CSCs) have roles in cancer chemoresistance, invasion, metastasis, and recurrence. Here, we investigated whether PEITC can suppress the properties of CSCs using NCCIT cells and HCT116-derived cancer stem-like cells. Furthermore, we established a CSC xenograft prevention model using nude mice.Purpose: The purpose of this study was to examine the actual cancer-preventive effects of PEITC in vitro and in a xenograft prevention model.Study Design: We assessed the cancer-preventive effects of PEITC on CSCs using a novel xenograft prevention model.Methods: NCCIT cells were treated with PEITC, and the expression of pluripotent markers was confirmed by reporter assays, western blotting, and qRT-PCR. In addition, to evaluate the effects of PEITC on CSC properties, sphere cells, which exhibit CSC properties, were established from the HCT116 cells. Furthermore, to examine the inhibitory effects and the underlying mechanism following daily intake of PEITC on CSCs, we performed an animal study in a mouse xenograft model and RNA-sequencing analysis.Results: PEITC significantly reduced the CSC properties, including clonogenicity and the expression of pluripotent factors. Prior to CSC inoculation in vivo, the PEITC pre-treatment group showed a more effective reduction in the tumor growth rate and expression of CSC markers compared to the post-treatment groups. Furthermore, RNA-sequencing results showed that PEITC pre-treatment remarkably suppressed genes related to inflammatory and immune responses and chemokine-related signaling.Conclusion: PEITC might contribute to the prevention or delay of colorectal cancer growth by inhibiting CSCs via the regulation of inflammatory chemokines, which can affect the tumor microenvironment. Thus, our study suggests that the daily intake of phytochemicals derived from vegetables or dietary supplements could have cancer-preventive effects through regulation of the host-tumor microenvironment. [ABSTRACT FROM AUTHOR]

Albumin is a serum transport protein, which has been utilized as a carrier for a variety of drugs to improve their delivery efficiency and to obtain favorable pharmacokinetic profiles. However, natural albumin possesses only a few high-affinity binding sites for a limited number of drugs. This results in deficiencies in drug-loading and serum stability, and consequently, in impaired therapeutic efficacy. Herein, BSA was modified with different isothiocyanate conjugates (BSA-ITCs), which self-assembled with paclitaxel (PTX) to produce BSA-ITCs/PTX nanoparticles. Among these BSA-ITCs, phenethyl isothiocyanate (PEITC)-modified BSA (BSA-PEITC35) conjugates effectively loaded PTX and formed highly stable BSA-PEITC35/PTX nanoparticles. Molecular modeling studies suggested that PEITC groups in BSA-PEITC35 can significantly lower the PTX binding free energy. BSA-PEITC35/PTX showed enhanced stability, prolonged blood circulation and increased tumor accumulation than unmodified BSA/PTX, and exerted more potent antitumor activity than both BSA/PTX and Abraxane in subcutaneous mouse tumor models after intravenous administration. Here, we designed phenethyl isothiocyanate (PEITC)-modified BSA (BSA-PEITC35) which self-assembled with paclitaxel (PTX) to form well-stabilized nanoparticles for effective cancer drug delivery. The introduction of PEITC moieties greatly lowered the binding energies of albumin and PTX, and led to greater drug loading and enhanced serum stability. BSA-PEITC35/PTX exhibited more efficient antitumor activity than both BSA/PTX and Abraxane, a clinically used albumin-stabilized PTX nanoparticle formulation. Thus, this strategy to introduce drug binding ligands in albumin is feasible and promising to develop effective albumin-based drug delivery system. Unlabelled Image [ABSTRACT FROM AUTHOR]