Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention

• Published in: PloS one Vol. 9; no. 12; p. e114764
• Main Authors: Bao, Yongping, Wang, Wei, Zhou, Zhigang, Sun, Changhao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.12.2014; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Antioxidants; Apoptosis; Biology and Life Sciences; Bladder; Bladder cancer; Caco-2 Cells; Cancer; Cancer prevention; Cell culture; Cell cycle; Cell death; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cells (Biology); Chemotherapy; Diabetes; Diet; Dietary Supplements; Disease prevention; Drug dosages; Endothelium - drug effects; Endothelium - metabolism; Enzymes; Fibroblasts; Gene expression; Health risks; Hep G2 Cells; Human Umbilical Vein Endothelial Cells; Humans; Isothiocyanate; Isothiocyanates - pharmacology; Isothiocyanates - therapeutic use; Medicine and Health Sciences; Neoplasms - prevention & control; Neovascularization, Physiologic - drug effects; NF-E2-Related Factor 2 - metabolism; Oxidative stress; Oxidative Stress - drug effects; Phagocytosis; Phytochemicals; Promotion; Risk Assessment; Risk factors; Rodents; Selenium; Selenium - pharmacology; Sulforaphane; Toxicology; Transcription factors; Tumors; Urinary bladder
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0114764

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.