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


METHODS
We 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.


RESULTS
The 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.


CONCLUSIONS
This 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.
Chen
Miao-Fen
MF
Department of Radiation Oncology, Chang Gung Memorial Hospital, Chia-Yi, Taiwan. miaofen@adm.cgmh.org.tw
Keng
Peter C
PC
Lin
Paul-Yang
PY
Yang
Cheng-Ta
CT
Liao
Shuen-Kuei
SK
Chen
Wen-Cheng
WC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D005347:Fibroblasts; D006801:Humans; D007249:Inflammation; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000096:biosynthesis / Q000502:physiology; D018384:Oxidative Stress; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives; D017564:Radiation Pneumonitis / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D002109:Caffeic Acids; D016328:NF-kappa B; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol