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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

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.

Conclusion

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.

Related collections

Most cited references 37

Record: found
Abstract: found
Article: not found

Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung.

P Sime, Z. Xing, F Graham … (1997)

Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of fibrosis based upon its matrix-inducing effects on stromal cells in vitro, and studies demonstrating increased expression of total TGF-beta1 in fibrotic tissues from a variety of organs. The precise role in vivo of this cytokine in both its latent and active forms, however, remains unclear. Using replication-deficient adenovirus vectors to transfer the cDNA of porcine TGF-beta1 to rat lung, we have been able to study the effect of TGF-beta1 protein in the respiratory tract directly. We have demonstrated that transient overexpression of active, but not latent, TGF-beta1 resulted in prolonged and severe interstitial and pleural fibrosis characterized by extensive deposition of the extracellular matrix (ECM) proteins collagen, fibronectin, and elastin, and by emergence of cells with the myofibroblast phenotype. These results illustrate the role of TGF-beta1 and the importance of its activation in the pulmonary fibrotic process, and suggest that targeting active TGF-beta1 and steps involved in TGF-beta1 activation are likely to be valuable antifibrogenic therapeutic strategies. This new and versatile model of pulmonary fibrosis can be used to study such therapies.

0 comments Cited 222 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis.

Yongjun Fan, M Simmons, Jérôme Kucharczak … (2003)

During their lifetime, cells encounter many life or death situations that challenge their very own existence. Their survival depends on the interplay within a complex yet precisely orchestrated network of proteins. The Rel/NF-kappaB signaling pathway and the transcription factors that it activates have emerged as critical regulators of the apoptotic response. These proteins are best known for the key roles that they play in normal immune and inflammatory responses, but they are also implicated in the control of cell proliferation, differentiation, apoptosis and oncogenesis. In recent years, there has been remarkable progress in understanding the pathways that activate the Rel/NF-kappaB factors and their role in the cell's decision to either fight or surrender to apoptotic challenge. Whereas NF-kappaB is most commonly involved in suppressing apoptosis by transactivating the expression of antiapoptotic genes, it can promote programmed cell death in response to certain death-inducing signals and in certain cell types. This review surveys our current understanding of the role of NF-kappaB in the apoptotic response and focuses on many developments since this topic was last reviewed in Oncogene 4 years ago. These recent findings shed new light on the activity of NF-kappaB as a critical regulator of apoptosis in the immune, hepatic, epidermal and nervous systems, on the mechanisms through which it operates and on its role in tissue development, homoeostasis and cancer.

0 comments Cited 138 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B.

Bharat B. Aggarwal, S. Singh, D Grunberger … (1996)

Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, is known to have antimitogenic, anticarcinogenic, antiinflammatory, and immunomodulatory properties. The molecular basis for these diverse properties is not known. Since the role of the nuclear factor NF-kappa B in these responses has been documented, we examined the effect of CAPE on this transcription factor. Our results show that the activation of NF-kappa B by tumor necrosis factor (TNF) is completely blocked by CAPE in a dose- and time-dependent manner. Besides TNF, CAPE also inhibited NF-kappa B activation induced by other inflammatory agents including phorbol ester, ceramide, hydrogen peroxide, and okadaic acid. Since the reducing agents reversed the inhibitory effect of CAPE, it suggests the role of critical sulfhydryl groups in NF-kappa B activation. CAPE prevented the translocation of the p65 subunit of NF-kappa B to the nucleus and had no significant effect on TNF-induced I kappa B alpha degradation, but did delay I kappa B alpha resynthesis. The effect of CAPE on inhibition of NF-kappa B binding to the DNA was specific, in as much as binding of other transcription factors including AP-1, Oct-1, and TFIID to their DNA were not affected. When various synthetic structural analogues of CAPE were examined, it was found that a bicyclic, rotationally constrained, 5,6-dihydroxy form was superactive, whereas 6,7-dihydroxy variant was least active. Thus, overall our results demonstrate that CAPE is a potent and a specific inhibitor of NF-kappa B activation and this may provide the molecular basis for its multiple immunomodulatory and antiinflammatory activities.

0 comments Cited 125 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): BMC Cancer

Title: BMC Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2407

Publication date Collection: 2005

Publication date (Electronic): 9 December 2005

Volume: 5

Page: 158

Affiliations

[1 ]Department of Radiation Oncology, Chang Gung Memorial Hospital, Chia-Yi, Taiwan

[2 ]Graduate Institute of Clinical Medical Science, Chang Gung University, Toyuan, Taiwan

[3 ]Department of Radiation Oncology, Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA

[4 ]Department of Pathology, Chang Gung Memorial Hospital, Chia-Yi, Taiwan

[5 ]Department of Internal medicine, Chang Gung Memorial Hospital, Chia-Yi, Taiwan

Article

Publisher ID: 1471-2407-5-158

DOI: 10.1186/1471-2407-5-158

PMC ID: 1325253

PubMed ID: 16336675

SO-VID: 6a0b572c-42a7-4707-b4e0-1853c6a64044

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

Read this article at

Abstract

Background

Methods

Results

Conclusion

Related collections

Karger: Oncology

Most cited references 37

Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung.

To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis.

Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B.

Author and article information

Journal

Affiliations

Article

History

Categories

Comments

Comment on this article

Similar content 90

Cited by 10

Most referenced authors 453