Lycopene acts through inhibition of IκB kinase to suppress NF-κB signaling in human prostate and breast cancer cells
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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.
KeywordsProstate cancer Breast cancer IκB kinase Lycopene NF-κB Nutrition
Nuclear factor kappa B
Inhibitor of kappa B
This study was funded by the Institute of Biomedical and Biomolecular Science (IBBS), University of Portsmouth. The authors thank DSM Nutritional Products for their generous gift of the lycopene used in the present study. The authors are also grateful to Mr. Salman Goudarzi, Miss Mikaella Vouri, and Mr. Phil Warren, School of Pharmacy and Biomedical Sciences, University of Portsmouth, for technical assistance.
EA and MCV performed the experiments, analyzed the results, and wrote the paper. MC and SH conceived of the study, designed the experiments, analyzed the results and wrote the paper.
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Conflicts of interest
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