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

Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention.
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DOI:
10.1371/journal.pone.0114764
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Sun C
Sun C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bao Y;Wang W;Zhou Z;Sun C

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在许多人类细胞系中,低水平(1-5 µM)的异硫氰酸酯(ITC)萝卜硫素(SFN)可促进细胞增殖至对照组的120-143%,而高水平(10-40 µM)时,它可抑制此类细胞增殖。对于细胞迁移观察到类似的剂量反应,即2.5 μM的SFN使膀胱癌T24细胞中的细胞迁移增加至128%,而高水平抑制细胞迁移。在血管生成试验中也发现了这种激素作用,其中2.5 µM的SFN促进内皮管形成(对照的118%),而在10-20 µM时则引起显著抑制。SFN影响促进细胞生长和迁移的确切机制尚不清楚,但可能涉及自噬的激活,因为自噬抑制剂3-甲基腺嘌呤消除了SFN对细胞迁移的影响。此外,低剂量的SFN提供了对自由基介导的细胞死亡的保护作用,这种作用通过与硒共同治疗而增强。这些结果表明,SFN可以防止或促进肿瘤细胞生长,这取决于剂量和靶细胞的性质。在正常细胞中,促进细胞生长可能是有益的,但在转化细胞或癌细胞中,它可能是不希望的风险因素。总之,ITC对细胞生长和迁移具有双相作用。ITCs的益处和风险不仅取决于剂量,还受与Se的相互作用和测量终点的影响。
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.
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