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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Tomato paste alters NF-κB and cancer-related mRNA expression in prostate cancer cells, xenografts, and xenograft
Marit Kolberg1, Sigrid Pedersen, Nasser E Bastani
1a Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine , University of Oslo , Oslo , Norway.
Abstract:
Tomatoes may protect against prostate cancer development, possibly through targeting signaling pathways such as nuclear factor-κB (NF-κB). We investigated whether tomato paste could modulate NF-κB activity and cancer-related gene expression in human derived prostate cancer cells (PC3) and PC3 xenografts. PC3-cells were stably transduced with an NF-κB-luciferase construct, and treated with tomato extracts or vehicle control. Nude mice bearing PC3 xenografts were fed a Western-like diet with or without 10% tomato paste for 6.5 wk. The tomato diet significantly inhibited TNFα stimulated NF-κB activity in cultured PC3 cells, and modulated the expression of genes associated with inflammation, apoptosis, and cancer progression. Accumulation of lycopene occurred in liver, xenografts, and serum of mice fed tomato diet. Tomato paste in the diet did not affect tumor size in mice; however, there was a trend toward inhibition of NF-κB activity in the xenografts. The effect of tomato on gene expression was most prominent in the xenograft microenvironment, where among others NFKB2, STAT3, and STAT6 showed higher expression levels after tomato treatment. Our findings support biological activity of tomatoes in cancer-related inflammation.
Insights
Tomatoes show biological activity against cancer-related inflammation by modulating nuclear factor-kappa B (NF-κB) signaling. This study investigated tomato paste
Area of Science:
- Oncology
- Nutritional Science
- Molecular Biology
Background:
- Prostate cancer development may be mitigated by tomatoes, potentially via nuclear factor-kappa B (NF-κB) signaling pathways.
- Understanding the molecular mechanisms of tomato's chemopreventive potential is crucial.
Purpose of the Study:
- To investigate the effects of tomato paste on NF-κB activity and cancer-related gene expression in prostate cancer cells and xenografts.
- To determine if dietary tomato paste influences NF-κB signaling and gene expression in vivo.
Main Methods:
- Human prostate cancer cells (PC3) with an NF-κB-luciferase construct were treated with tomato extracts.
- Mice bearing PC3 xenografts were fed a Western-like diet with or without 10% tomato paste.
- NF-κB activity, gene expression, and lycopene accumulation were analyzed.
Main Results:
- Tomato diet significantly inhibited TNFα-stimulated NF-κB activity in cultured PC3 cells.
- Dietary tomato paste modulated genes related to inflammation, apoptosis, and cancer progression in xenografts.
- Lycopene accumulated in tissues and serum of mice on the tomato diet; NF-κB activity showed a trend toward inhibition in xenografts.
Conclusions:
- Tomatoes possess biological activity relevant to cancer-related inflammation.
- Tomato consumption may influence key signaling pathways and gene expression in the tumor microenvironment.
- Further research into tomato-based cancer prevention strategies is warranted.
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