PARENT SESSION

Experimental and Clinical Therapeutics

(PP147) Topically applied green tea extracts to treat radiation-induced skin toxicity - involvement of a caspase-dependent mechanism.

Pajonk, Frank^*,1, Riedisser, Anja ², McBride, William¹, Fiebich, Bernd³, ¹ Department of Radiation Onoclogy, Los Angeles, CA, USA² Department of Radiation Oncology, Freiburg, BW, Germany³ Department of Psychiatry, Freiburg, BW, Germany

ABSTRACT- Introduction & Objectives: Skin toxicity is a common side effect of radiotherapy for solid tumors. Its management may cause treatment gaps und thus may reduce tumor control probability. At present, no standard treatment recommendation for skin treatment during radiotherapy exists. In this study, we explored the effect of topically applied tea extracts on the duration of radiation-induced skin toxicity. We investigated the underlying molecular mechanisms and compared effects of tea extracts with the effects of epigallocatechin-gallate, the proposed most active moiety of green tea. Material & Methods: Data from 60 patients with cancer of the head and neck or pelvic region topically treated with green or black tea extracts were analyzed. Tea extracts were compared for their ability to modulate IL-1, IL-6, IL-8, TNF and PGE2 release from human monocytes. Effects of tea extracts on 26S proteasome function were assessed. NF-B and AP-1 DNA-binding activity were monitored by EMSA′s. Viability and radiation response of macrophages after exposure to tea extracts was measured by MTT-assays. Results: Green tea extracts supported the restitution of skin integrity. Tea extracts inhibited proteasome function and suppressed cytokine release. NF-B and AP-1 DNA-binding activity were altered by tea extracts in a complex, caspase-dependent manner, which differed from effects of epigallocatechin-gallate. Additionally, both tea extracts as well as epigallocatechin-gallate slightly protected macrophages from ionizing radiation. Conclusions: Green tea extracts are an efficient, broadly available treatment option for patients suffering from acute radiation-induced skin toxicity. The molecular mechanisms underlying the beneficial effects are complex and most likely not exclusively dependent on effects of tea polyphenols like epigallocatechin-gallate.

Key words: Tea polyphenols, skin reaction, NF-kB, proteasome