title: Enhanced in vitro biological activity of synthetic 2-(2-pyridyl) ethyl isothiocyanate compared to natural 4-(methylsulfinyl) butyl isothiocyanate.
abstract: Dietary isothiocyanates (ITC) derived from cruciferous vegetables have been shown to have numerous biological effects consistent with chemoprotective activity. In this study we synthesized a novel ITC, 2-(2-pyridyl) ethyl ITC (PY-ITC), and assessed its chemopreventive ability in comparison to sulforaphane (SF), the ITC derived from broccoli. PY-ITC suppressed cancerous cell growth and proliferation at lower concentrations than SF and was more potent at inducing p21 protein. Through the use of whole genome arrays we demonstrate that prostate cells exposed to PY-ITC or SF have similar biological response, albeit PY-ITC alters a greater number of genes, and to a greater extent. In the presence of a phosphatidylinositol-3-kinase (PI3K) inhibitor PY-ITC had a more pronounced effect on gene expression, emphasizing the important role of PI3K/AKT signaling in mediating the chemopreventive effects of ITCs. These results highlight the importance of the ITC side chain in bioactivity.
authors.affiliation: Food & Health Programme,  Institute of Food Research , Norwich Research Park, NR4 7UA United Kingdom.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Melchini
authors.forename: Paul W
authors.initials: PW
authors.lastname: Needs
authors.forename: Richard F
authors.initials: RF
authors.lastname: Mithen
authors.forename: Maria H
authors.initials: MH
authors.lastname: Traka
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001937:Brassica / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004032:Diet; D020869:Gene Expression Profiling; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction; D013454:Sulfoxides; D013861:Thiocyanates / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; C039155:ethyl isothiocyanate; C039156:butyl isothiocyanate; C016766:sulforaphane