Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 55, Issue 22, Pages 9682-9692Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm300929v
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Funding
- Plant Bioscience Limited (PBL)
- Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme
- Biotechnology and Biological Sciences Research Council [BBS/E/F/00044431] Funding Source: researchfish
- BBSRC [BBS/E/F/00044431] Funding Source: UKRI
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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.
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