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Tumour Biol. 2016 Jul;37(7):9375-85. doi: 10.1007/s13277-016-4798-3. Epub 2016 Jan 16.

Lycopene acts through inhibition of IκB kinase to suppress NF-κB signaling in human prostate and breast cancer cells.

Author information

1
Institute of Biomedical and Biomolecular Science (IBBS), School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael's Building, White Swan Road, PO1 2DT, Portsmouth, UK.
2
Institute of Biomedical and Biomolecular Science (IBBS), School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael's Building, White Swan Road, PO1 2DT, Portsmouth, UK. sassan.hafizi@port.ac.uk.

Abstract

We studied the effect of the potent dietary antioxidant lycopene on multiple points along the nuclear factor kappa B (NF-κB) signaling pathway in prostate and breast cancer cells. Lycopene significantly inhibited prostate and breast cancer cell growth at physiologically relevant concentrations of ≥1.25 μM. Similar concentrations also caused a 30-40 % reduction in inhibitor of kappa B (IκB) phosphorylation in the cells, as determined by western blotting. Furthermore, the same degree of inhibition by lycopene was observed for NF-κB transcriptional activity, as determined by reporter gene assay. Concomitant with this, immunofluorescence staining of lycopene-treated cells showed a significant suppression (≥25 %) of TNF-induced NF-κB p65 subunit nuclear translocation. Further probing of lycopene's effects on upstream elements of the NF-κB pathway showed a 25 % inhibition of both activity of recombinant IκB kinase β (IKKβ) kinase in a cell-free in vitro assay, as well as activity of IKKβ immunoprecipitated from MDA-MB-231 cells treated with lycopene. In conclusion, the anticancer properties of lycopene may occur through inhibition of the NF-κB signaling pathway, beginning at the early stage of cytoplasmic IKK kinase activity, which then leads to reduced NF-κB-responsive gene regulation. Furthermore, these effects in cancer cells were observed at concentrations of lycopene that are relevant and achievable in vivo.

KEYWORDS:

Breast cancer; IκB kinase; Lycopene; NF-κB; Nutrition; Prostate cancer

PMID:
26779636
DOI:
10.1007/s13277-016-4798-3
[Indexed for MEDLINE]

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