The effects of tea extracts on proinflammatory signaling.
BACKGROUND
Skin toxicity is a common side effect of radiotherapy for solid tumors. Its management can cause treatment gaps and thus can impair cancer treatment. At present, in many countries no standard recommendation for treatment of skin 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.


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 retrospectively. Tea extracts were compared for their ability to modulate IL-1beta, IL-6, IL-8, TNFalpha and PGE2 release from human monocytes. Effects of tea extracts on 26S proteasome function were assessed. NF-kappaB activity was monitored by EMSAs. Viability and radiation response of macrophages after exposure to tea extracts was measured by MTT assays.


RESULTS
Tea extracts supported the restitution of skin integrity. Tea extracts inhibited proteasome function and suppressed cytokine release. NF-kappaB activity was altered by tea extracts in a complex, caspase-dependent manner, which differed from the effects of epigallocatechin-gallate. Additionally, both tea extracts, as well as epigallocatechin-gallate, slightly protected macrophages from ionizing radiation


CONCLUSIONS
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 such as epigallocatechin-gallate.
Pajonk
Frank
F
Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1714, USA. fpajonk@mednet.ucla.edu
Riedisser
Anja
A
Henke
Michael
M
McBride
William H
WH
Fiebich
Bernd
B
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D028241:Camellia sinensis; D002460:Cell Line; D016207:Cytokines / Q000187:drug effects*; D004247:DNA / Q000187:drug effects; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D016328:NF-kappa B / Q000187:drug effects*; D009369:Neoplasms / Q000532:radiotherapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D061988:Proteasome Inhibitors; D011832:Radiation Injuries / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D011878:Radiotherapy / Q000009:adverse effects; D012867:Skin / Q000528:radiation effects; D012871:Skin Diseases / Q000209:etiology / Q000628:therapy
D016207:Cytokines; D016328:NF-kappa B; D010936:Plant Extracts; D061988:Proteasome Inhibitors; D004247:DNA