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

Bao Y, Wang W, Zhou Z, Sun C - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.

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.

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Related in: MedlinePlus

Effects of SFN and 3-MA on cell migration.A: After starvation overnight, bladder cancer T24 cells were treated with SFN at the concentrations indicated for 24 h, cell migration was measured by a cell migration assay using the ThinCert cell culture inserts (Greiner Bio-One Ltd.). Each bar represents the mean ± SD of 3 replicates. B: Effect of pre-treatment of 3-MA on cell migration. DMSO (0.1% was used as a control). Statistical significance from the control, *p<0.05, or **p<0.01.
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pone-0114764-g002: Effects of SFN and 3-MA on cell migration.A: After starvation overnight, bladder cancer T24 cells were treated with SFN at the concentrations indicated for 24 h, cell migration was measured by a cell migration assay using the ThinCert cell culture inserts (Greiner Bio-One Ltd.). Each bar represents the mean ± SD of 3 replicates. B: Effect of pre-treatment of 3-MA on cell migration. DMSO (0.1% was used as a control). Statistical significance from the control, *p<0.05, or **p<0.01.

Mentions: Fig. 2A shows a bell-shaped dose response of SFN on bladder cancer T24 cell migration. SFN at 2.5 and 3.75 µM increased tumour cell migration to 128 and 133% in comparison with corresponding controls. Such SFN-induced cell migration is associated with the ability of SFN to activate autophagy. When an autophagy inhibitor, 3-methyladenine (3-MA), was used it alleviated SFN (2.5 µM)-induced cell migration from 128 to 26% although it has less inhibitory effect on SFN treatments at 5 or 10 µM (Fig. 2B). Moreover, 3-MA also decreased the migration of non-SFN treated cells to 12% of the control.


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

Bao Y, Wang W, Zhou Z, Sun C - PLoS ONE (2014)

Effects of SFN and 3-MA on cell migration.A: After starvation overnight, bladder cancer T24 cells were treated with SFN at the concentrations indicated for 24 h, cell migration was measured by a cell migration assay using the ThinCert cell culture inserts (Greiner Bio-One Ltd.). Each bar represents the mean ± SD of 3 replicates. B: Effect of pre-treatment of 3-MA on cell migration. DMSO (0.1% was used as a control). Statistical significance from the control, *p<0.05, or **p<0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4273949&req=5

pone-0114764-g002: Effects of SFN and 3-MA on cell migration.A: After starvation overnight, bladder cancer T24 cells were treated with SFN at the concentrations indicated for 24 h, cell migration was measured by a cell migration assay using the ThinCert cell culture inserts (Greiner Bio-One Ltd.). Each bar represents the mean ± SD of 3 replicates. B: Effect of pre-treatment of 3-MA on cell migration. DMSO (0.1% was used as a control). Statistical significance from the control, *p<0.05, or **p<0.01.
Mentions: Fig. 2A shows a bell-shaped dose response of SFN on bladder cancer T24 cell migration. SFN at 2.5 and 3.75 µM increased tumour cell migration to 128 and 133% in comparison with corresponding controls. Such SFN-induced cell migration is associated with the ability of SFN to activate autophagy. When an autophagy inhibitor, 3-methyladenine (3-MA), was used it alleviated SFN (2.5 µM)-induced cell migration from 128 to 26% although it has less inhibitory effect on SFN treatments at 5 or 10 µM (Fig. 2B). Moreover, 3-MA also decreased the migration of non-SFN treated cells to 12% of the control.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.

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.

Show MeSH
Related in: MedlinePlus