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

Giallourou, Natasa S., Rowland, Ian R., Rothwell, Steve D., Packham, Graham, Commane, Daniel M. and Swann, Jonathan R. (2019) Metabolic targets of watercress and PEITC in MCF-7 and MCF-10A cells explain differential sensitisation responses to ionising radiation. European Journal of Nutrition, 58 (6). pp. 2377-2391. ISSN 1436-6207

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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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