title: Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention.
abstract: The isothiocyanate (ITC) sulforaphane (SFN) was shown at low levels (1-5 µM) to promote cell proliferation to 120-143% of the controls in a number of human cell lines, whilst at high levels (10-40 µM) it inhibited such cell proliferation. Similar dose responses were observed for cell migration, i.e. SFN at 2.5 µM increased cell migration in bladder cancer T24 cells to 128% whilst high levels inhibited cell migration. This hormetic action was also found in an angiogenesis assay where SFN at 2.5 µM promoted endothelial tube formation (118% of the control), whereas at 10-20 µM it caused significant inhibition. The precise mechanism by which SFN influences promotion of cell growth and migration is not known, but probably involves activation of autophagy since an autophagy inhibitor, 3-methyladenine, abolished the effect of SFN on cell migration. Moreover, low doses of SFN offered a protective effect against free-radical mediated cell death, an effect that was enhanced by co-treatment with selenium. These results suggest that SFN may either prevent or promote tumour cell growth depending on the dose and the nature of the target cells. In normal cells, the promotion of cell growth may be of benefit, but in transformed or cancer cells it may be an undesirable risk factor. In summary, ITCs have a biphasic effect on cell growth and migration. The benefits and risks of ITCs are not only determined by the doses, but are affected by interactions with Se and the measured endpoint.
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom; Department of Cardiovascular Medicine, Affiliated hospital of Nantong University, Nantong, Jiangsu, P. R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: School of Public Health, Harbin Medical University, Harbin, Heilongjiang, P. R. China.
authors.forename: Changhao
authors.initials: C
authors.lastname: Sun
mesh_terms: D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019587:Dietary Supplements; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology* / Q000627:therapeutic use; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009369:Neoplasms / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D018570:Risk Assessment; D012643:Selenium / Q000494:pharmacology
chemical_list: D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012643:Selenium