title: Lycopene acts through inhibition of IκB kinase to suppress NF-κB signaling in human prostate and breast cancer cells.
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.
authors.affiliation: 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.
authors.forename: Emelia A
authors.initials: EA
authors.lastname: Assar
authors.affiliation: 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.
authors.forename: Magdalena Castellano
authors.initials: MC
authors.lastname: Vidalle
authors.affiliation: 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.
authors.forename: Mridula
authors.initials: M
authors.lastname: Chopra
authors.affiliation: 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.
authors.forename: Sassan
authors.initials: S
authors.lastname: Hafizi
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002338:Carotenoids / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D000077276:Lycopene; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D016588:Anticarcinogenic Agents; D016328:NF-kappa B; D002338:Carotenoids; D051550:I-kappa B Kinase; D000077276:Lycopene
keywords: Breast cancer; IκB kinase; Lycopene; NF-κB; Nutrition; Prostate cancer