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31.07.2018 | Original Contribution Open Access

Metabolic targets of watercress and PEITC in MCF-7 and MCF-10A cells explain differential sensitisation responses to ionising radiation

Zeitschrift:
European Journal of Nutrition
Autoren:
Natasa S. Giallourou, Ian R. Rowland, Steve D. Rothwell, Graham Packham, Daniel M. Commane, Jonathan R. Swann
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00394-018-1789-8) contains supplementary material, which is available to authorized users.

Abstract

Purpose

Watercress is a rich source of phytochemicals with anticancer potential, including phenethyl isothiocyanate (PEITC). We examined the potential for watercress extracts and PEITC to increase the DNA damage caused by ionising radiation (IR) in breast cancer cells and to be protective against radiation-induced collateral damage in healthy breast cells. The metabolic events that mediate such responses were explored using metabolic profiling.

Methods

1H nuclear magnetic resonance spectroscopy-based metabolic profiling was coupled with DNA damage-related assays (cell cycle, Comet assay, viability assays) to profile the comparative effects of watercress and PEITC in MCF-7 breast cancer cells and MCF-10A non-tumorigenic breast cells with and without exposure to IR.

Results

Both the watercress extract and PEITC-modulated biosynthetic pathways of lipid and protein synthesis and resulted in changes in cellular bioenergetics. Disruptions to the redox balance occurred with both treatments in the two cell lines, characterised by shifts in the abundance of glutathione. PEITC enhanced the sensitivity of the breast cancer cells to IR increasing the effectiveness of the cancer-killing process. In contrast, watercress-protected non-tumorigenic breast cells from radiation-induced damage. These effects were driven by changes in the cellular content of the antioxidant glutathione following exposure to PEITC and other phytochemicals in watercress.

Conclusion

These findings support the potential prophylactic impact of watercress during radiotherapy. Extracted compounds from watercress and PEITC differentially modulate cellular metabolism collectively enhancing the therapeutic outcomes of radiotherapy.

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Zusatzmaterial
Fig. S1: (a) Correlation coefficients plot obtained from the OPLS-DA model identifying metabolic changes in the MCF-7 cells induced by 5 Gy of IR exposure. (b) OPLS-DA model constructed on the metabolic profiles of cell extracts obtained from control and irradiated (5 Gy IR exposure) MCF-10A cells (c) OPLS-DA coefficients plot comparing the metabolic profiles of untreated control MCF-7 cells and the highest dose of WX (50 μl/ml) treated cells. (d) OPLS-DA coefficients plot comparing the metabolic profiles of untreated control MCF-7 cells and PEITC (20 μM) treated cells. (e) OPLS-DA coefficients plot comparing the metabolic profiles of untreated control MCF-10A cells and the highest dose of WX (50 μl/ml) treated cells. (f) OPLS-DA coefficients plot comparing the metabolic profiles of untreated control MCF-10A cells and PEITC (20 μM) treated cells. AXP: indistinguishable difference between AMP, ADP, ATP, GPC, glycerophosphocholine (DOCX 279 KB)
394_2018_1789_MOESM1_ESM.docx
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