C: HHL-5 cell were pre-treated with SFN (2 M) and Se (0.1 M) for 24 h before exposure to H2O2(400 M) for a further 24 h. 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 malignancy cells it may be BCI-121 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. == Introduction == The term hormesis is often used by toxicologists to refer to a biphasic dose response to an environmental agent characterized by low dose activation and by high dose inhibitory or harmful effect[1],[2]. Rabbit Polyclonal to FCGR2A The hormesis concept is the most fundamental dose-response relationship in the biomedical, nutrition and toxicological sciences[1]. In a comprehensive review, Calabrese provided evidence that more BCI-121 than a hundred anti-tumour brokers enhanced the proliferation of human tumour cells at low doses in BCI-121 a manner fully consistent with the hormetic dose-response relationship[2]. One of the interesting characteristics of such dose-responses was that they occurred in most types of tumour cells and were independent of organ. Recent findings suggest that some phytochemicals exhibit biphasic dose responses in cells with low doses activating signalling pathways that result in increased expression of genes encoding cytoprotective proteins and antioxidant enzymes[3]. The dietary hormetic compounds recognized so far include resveratrol, epigallocatechin gallate (EGCG), curcumin, quercetin, allicin, capsaicin, carnosic acid and sulforaphane (SFN)[4][8]. From an evolutionary perspective, the noxious properties of phytochemicals have an important protective role in dissuading insects and fungi from damaging plants. However, the relatively small doses of phytochemicals ingested by humans that consume these plants are not harmful and instead induce mild cellular stress responses. This phenomenon has been widely described as hormesis or adaptive dose response in the fields of biology and medicine[4],[9],[10]. The isothiocyanate (ITC), SFN (4-methylsulfinylbutylisothiocyanate), was first isolated from your commonly-consumed cruciferous vegetable, broccoli and is one of the most potent naturally-occurring inducers of the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response elements (ARE) pathway[11]. The induction of Nrf2 protects normal cells from free-radical mediated oxidative stress via upregulation of chemoprotective genes, and the action of SFN is based on its ability to induce a Nrf2-driven enzyme quinone reductase (NQO1)[12]. In the 20 years subsequent to its discovery, the protective effects of SFN have been exhibited in various cell culture systems and animal models, with the result that SFN is usually by far the most extensively analyzed ITC from cruciferous vegetables. The anti-carcinogenic mechanisms of ITCs have also been well-documented, including up-regulation of phase II detoxification enzymes, anti-inflammation, promotion of cell cycle arrest and apoptosis[13][17]. During the last decade, Keap1-Nrf2-ARE has been considered as a critical anti-cancer pathway in chemoprevention[18]-[20]. However, more recently, there have been some deleterious reports of Nrf2, including promotion of tumour cell growth and chemoresistance[21][25]. In order to survive, malignancy cells may hijack the Nrf2 pathway which upregulates a battery of antioxidant enzymes, thereby maintaining a favourable redox balance in order to acquire malignant properties[26]. Overexpression of Nrf2 could enhance cell proliferation and cause resistance to chemotherapeutic interventions in some types of malignancy, including human lung and pancreatic cancers[27],[28]. A few previous investigations have shown that SFN exhibits a dose-dependent effects on cell proliferation in cultured tumour cell lines and normal cells including human mesenchymal stem cells[29][31]. In the present study, we showed that SFN exhibited a hormetic dose response on cell growth, migration and angiogenesis. Whether the hormetic effect is beneficial or harmful depends on the selected endpoint and/or the nature of the cells (normal or tumour). Although the term hormesis is employed by toxicologists.