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

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


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.

MeSH terms

  • Anticarcinogenic Agents / pharmacology
  • Apoptosis / drug effects
  • Blotting, Western
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carotenoids / pharmacology*
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects*
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • I-kappa B Kinase / antagonists & inhibitors*
  • I-kappa B Kinase / metabolism
  • Immunoenzyme Techniques
  • Immunoprecipitation
  • Lycopene
  • Male
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured


  • Anticarcinogenic Agents
  • NF-kappa B
  • Carotenoids
  • I-kappa B Kinase
  • Lycopene