Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation in vitro and in vivo

Miao-Fen Chen,Shuen-Kuei Liao,Peter C Keng,Paul-Yang Lin,Cheng-Ta Yang,Wen-Cheng Chen

doi:10.1186/1471-2407-5-158

Miao-Fen Chen, Shuen-Kuei Liao + Show 4 more

Open Access

https://doi.org/10.1186/1471-2407-5-158

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Abstract

BackgroundLung cancer is relatively resistant to radiation treatment and radiation pneumonitis is a major obstacle to increasing the radiation dose. We previously showed that Caffeic acid phenethyl ester (CAPE) induces apoptosis and increases radiosensitivity in lung cancer. To determine whether CAPE, an antioxidant and an inhibitor of NF-kappa B, could be a useful adjuvant agent for lung cancer treatment, we examine the effects of CAPE on irradiated normal lung tissue in this study.MethodsWe compared the effects of CAPE on cytotoxicity and intracellular oxidative stress in normal lung fibroblast and a lung cancer cell line. For in vivo analysis, whole thorax radiation (single dose 10 Gy and 20 Gy) was delivered to BALB/c male mice with or without CAPE pretreatment. NF- kappaB activation and the expression levels of acute inflammatory cytokines were evaluated in mice after irradiation.ResultsThe in vitro studies showed that CAPE cause no significant cytotoxicity in normal lung as compared to lung cancer cells. This is probably due to the differential effect on the expression of NF-kappa B between normal and malignant lung cells. The results from in vivo study showed that CAPE treatment decreased the expression of inflammatory cytokines including IL-1 alpha and beta, IL-6, TNF-alpha and TGF- beta, after irradiation. Moreover, histological and immunochemical data revealed that CAPE decreased radiation- induced interstitial pneumonitis and TGF-beta expression.ConclusionThis study suggests that CAPE decreases the cascade of inflammatory responses induced by thoracic irradiation without causing toxicity in normal lung tissue. This provides a rationale for combining CAPE and thoracic radiotherapy for lung cancer treatment in further clinical studies.

Highlights

Lung cancer is relatively resistant to radiation treatment and radiation pneumonitis is a major obstacle to increasing the radiation dose
Caffeic acid phenethyl ester (CAPE) causes no cytotoxicity or radiosensitization in normal lung cells In our previous report, we demonstrated that 6 μg/ml CAPE caused significant cytotoxicity and increased apoptosis in lung cancer cells [5]
The percentage apoptosis showed no obvious increase in WI-38 after CAPE treatment

Summary

Introduction

Lung cancer is relatively resistant to radiation treatment and radiation pneumonitis is a major obstacle to increasing the radiation dose. Because radiation pneumonitis is a major obstacle to increasing the radiation dose, it is important to determine how the incidence of radiation- induced complication might be decreased and how the dose that normal lung can tolerate might be increased. CAPE is an active anti-inflammatory compound [11,12], and a specific inhibitor of the transcription factor nuclear factor-κB (NFκB) [13,14] It might play a role in protecting normal tissue against damage from radiation treatment. We were interested in evaluating the effects of CAPE on the intracellular ROS and NF-κB activation in these cells Another important goal of this study was to evaluate the efficiency of CAPE in an animal model of radiation- induced pneumonitis

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Conclusion