Activity Of Phenethyl Isothiocyanate Research Articles

Naturally Derived Phenethyl Isothiocyanate Modulates Induction of Oxidative Stress via Its N-Acetylated Cysteine Conjugated form in Malignant Melanoma.

Phenethyl isothiocyanate (PEITC) is a secondary metabolic product yielded upon the hydrolysis of gluconasturtiin and it is highly accumulated in the flowers of watercress. The aim of the current study was to assess the role of a naturally derived PEITC-enriched extract in the induction of oxidative stress and to evaluate its anti-melanoma potency through the regulation of its metabolism with the concurrent production of the N-acetyl cysteine conjugated by-product. For this purpose, an in vitro melanoma model was utilized consisting of human primary (A375) cells as well as metastatic (COLO-679) malignant melanoma cells together with non-tumorigenic immortalized keratinocytes (HaCaT). Cytotoxicity was assessed via the Alamar Blue assay whereas the antioxidant/prooxidant activity of PEITC was determined via spectrophotometric assays. Finally, kinetic characterization of the end-product of PEITC metabolism was monitored via UPLC coupled to a tandem mass spectrometry (MS/MS). Our results indicate that although PhEF showed very minor antioxidant activity in a cell-free system, in a cell-based system, it can modulate the activity of key enzyme(s) involved in cellular antioxidant defense mechanism(s). In addition, we have shown that PhEF induces lipid and protein oxidation in a concentration-dependent manner, while its cytotoxicity is not only dependent on PEITC itself but also on its N-acetylated cysteine conjugated form.

Abstract 568: Biomarkers of phenethyl isothiocyanate-mediated mammary cancer prevention in MMTV-neu mouse model

Abstract Biomarker(s) predictive of efficacy is necessary for clinical development of promising cancer chemopreventive agents because cancer incidence is too rigorous of an end point for malignancies with long latency such as breast cancer. The present study was undertaken to identify biomarker(s) associated with phenethyl isothiocyanate (PEITC)-mediated mammary cancer prevention in MMTV-neu transgenic mouse model. The PEITC is a promising cancer chemopreventive constituent of cruciferous vegetables (e.g., watercress). Two-dimensional gel electrophoresis-mass spectrometry of tumor specimens from control and PEITC-fed mice (n= 3) revealed alterations in expression of several proteins, including hexokinase-1, isoform CRA_f (1.36-fold increase by PEITC administration), L-lactate dehydrogenase A chain isoform 1 (1.57-fold increase by PEITC administration), pyruvate kinase isozymes M1/M2 (1.33-fold decrease by PEITC administration), and mitochondrial ATP synthase, H+ transporting F1 complex beta subunit (1.38-fold decrease by PEITC administration). Interestingly, the PEITC-induced apoptotic cell death in cultured cancer cells is associated with inhibition of oxidative phosphorylation leading to production of reactive oxygen species. Down-regulation of mitochondrial ATP synthase protein in tumors of PEITC-fed mice was confirmed by immunohistochemistry. Expression of mitochondrial ATP synthase was reduced by about 66% in the tumors from PEITC-fed mice in comparison with control (P= 0.05 by two-sided Student's t-test, n= 6-7). In addition, plasma level of transthyretin was significantly higher in the PEITC treatment group compared with control (P= 0.04 by two-sided Student's t-test, n= 5). In conclusion, the present study not only underscores the power of proteomics in cancer chemoprevention research but also suggests that mitochondrial ATP synthase, and possibly hexokinase-1, pyruvate kinase isozymes M1/M2, and/or L-lactate dehydrogenase A chain isoform 1, may be useful biomarkers to assess the biological activity of PEITC in future clinical trials. This study was supported in part by the US PHS grants CA101753 and CA129347, awarded by the National Cancer Institute. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 568. doi:1538-7445.AM2012-568

Antimicrobial activities of phenethyl isothiocyanate isolated from horseradish

Phenethyl isothiocyanate (PEITC) was obtained from horseradish. The preparation procedure was as follows: the horseradish powder was hydrolysed in the water first, and then, after filtration, the residue was extracted by petroleum ether; finally, PEITC was isolated by silica gel column. The structure of PEITC was identified by IR, MS, 1H-NMR and 13C-NMR chromatography methods. The inhibitory activities of PEITC against Gibberella zeae, Xanthomonas axonopodis pv. citri, Cytospora sp. and Phytophthora capsisi showed that PEITC had good inhibition effects. The EC50 values of G. zeae, X. axonopodis pv. citri, Cytospora sp. and P. capsisi were 13.92, 1.20, 0.73 and 3.69 µg mL−1, respectively.

Phenethyl isothiocyanate suppresses nitric oxide production via inhibition of phosphoinositide 3‐kinase/Akt‐induced IFN‐γ secretion in LPS‐activated peritoneal macrophages

Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables, is well known to have versatile physiological activities, including chemopreventive effects. On the other hand, its anti-inflammatory effects are poorly reported. Nitric oxide (NO) is associated with a wide variety of inflammatory diseases. In this study, we investigated the effects of PEITC on NO production in LPS-activated peritoneal macrophages from ICR mice. The signaling pathway of LPS-induced NO production was examined using neutralizing antibodies [anti-interferon (IFN)-gamma and anti-interleukin (IL-12)] and specific protein kinase inhibitors, as well as others. The activity of PEITC toward NOx production was assessed in mice that received LPS via intraperitoneal administration. The neutralizing antibody of anti-IFN-gamma, but not anti-IL-12, suppressed LPS-induced NO production by 90%. LY294002, a specific inhibitor of phosphoinositide-3-kinase, suppressed Akt and IFN-gamma mRNA expression up-regulated by LPS, whereas PEITC exhibited a similar inhibition profile. Furthermore, oral administration of PEITC significantly suppressed the serum concentration of NOx in ICR mice. Our results suggest that PEITC suppresses LPS-induced NO production via inhibition of Akt activation and the resultant decrease in expression of IFN-gamma. This is one of the first reports to demonstrate a marked anti-inflammatory effect of PEITC following its oral administration.

Antibacterial Activities of Phenethyl Isothiocyanate and Its Derivatives against Human Oral Pathogens

The antibacterial activity of Sinapis alba seed oils was tested against oral bacteria. The active constituent of S. Alba oil was identified as phenethyl isothiocyanate. Phenethyl isothiocyanate showed strong and moderate inhibition at 0.75 and 0.5 mg/disc, respectively, against Porphyromonas asaccharolytica, P. gingivalis and Streptococcus sobrinus. Similarly, benzoyl isothiocyanate and benzyl isothiocyanate had moderate inhibition at 0.5 mg/disc against P. asaccharolytica, P. gingivalis and S. Sobrinus. These results indicate that the effectiveness of isothiocyanate derivatives against oral pathogens is related to their aromatic structure.