Combined administration of EGCG and IL-1 receptor antagonist efficiently downregulates IL-1-induced tumorigenic factors in U-2 OS human osteosarcoma cells

Hönicke,Anne-Sophie; Ender,Stephan  Albrecht; Radons,Jürgen

doi:10.3892/ijo.2012.1498

Combined administration of EGCG and IL-1 receptor antagonist efficiently downregulates IL-1-induced tumorigenic factors in U-2 OS human osteosarcoma cells

Authors:
- Anne-Sophie Hönicke
- Stephan Albrecht Ender
- Jürgen Radons
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Affiliations: Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, D-17475 Greifswald, Germany, Department of Orthopaedics and Orthopaedic Surgery, University Medicine Greifswald, D-17475 Greifswald, Germany
Published online on: May 28, 2012 https://doi.org/10.3892/ijo.2012.1498
Pages: 753-758

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Abstract

Chronic inflammation represents one of the hallmarks of cancer. Of special relevance to the malignant process is the pro-inflammatory cytokine IL-1 playing a crucial role in cancer-related inflammation. Recent observations indicate increased IL-1 levels in an animal model of human osteosarcoma, the most frequent primary malignant bone tumor in man. In patients with bone sarcomas, increased serum levels of tumor-promoting cytokines, including IL-6, IL-8 and VEGF can be found, correlating with poor overall survival. The link between cancer and inflammation makes it clear that there is a need to reduce the external factors inducing inflammation as a preventive or therapeutical measure. Therefore, in the present study the effects of anti-inflammatory IL-1 receptor antagonist (IL-1Ra) was tested alone and in combination with (-)-epigallocatechin-3-gallate (EGCG), an anti-inflammatory chemopreventive agent from green tea, on the production of IL-1-induced tumorigenic factors in U-2 OS human osteosarcoma cells. We found that IL-1Ra and EGCG downregulated IL-1-induced IL-6 and IL-8 release from U-2 OS cells by 65-85%. IL-1Ra and EGCG also reduced secretion of invasiveness-promoting MMP-2 and pro-angiogenic VEGF to 62-75% without affecting the metabolic response and caspase-3 activity. In conclusion, downregulation of IL-1-induced tumorigenic factors (IL-6, IL-8, VEGF, MMP-2) in U-2 OS by IL-1Ra and EGCG may positively affect tumor-associated inflammation and, as a consequence, lead to reduction in angiogenesis and invasiveness. This renders a combined administration of EGCG and IL-1Ra a promising approach as an adjuvant therapy in patients with osteosarcoma.

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