The potential usage of caffeic acid phenethyl ester (CAPE) against chemotherapy-induced and radiotherapy-induced toxicity Sumeyya Akyol 1 , Zeynep Ginis 2 , Ferah Armutcu 1 , Gulfer Ozturk 2 , M. Ramazan Yigitoglu 1 and Omer Akyol 3,4 * 1 Department of Biochemistry, Fatih University Medical School, Ankara, Turkey 2 Department of Clinical Biochemistry, Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey 3 Department of Biochemistry, Hacettepe University Medical School, Ankara, Turkey 4 Department of Chemistry, Ankara Branch of Council of Forensic Medicine, Ankara, Turkey Protection of the patients against the side effects of chemotherapy and radiotherapy regimens has attracted increasing interest of clinicians and practitioners. Caffeic acid phenethyl ester (CAPE), which is extracted from the propolis of honeybee hives as an active component, specifically inhibits nuclear factor kB at micromolar concentrations and show ability to stop 5-lipoxygenase-catalysed oxygenation of linoleic acid and arachidonic acid. CAPE has antiinflammatory, antiproliferative, antioxidant, cytostatic, antiviral, antibacterial, antifungal and antineoplastic properties. The purpose of this review is to summarize in vivo and in vitro usage of CAPE to prevent the chemotherapy-induced and radiotherapy-induced damages and side effects in experimental animals and to develop a new approach for the potential usage of CAPE in clinical trial as a protective agent during chemotherapy and radiotherapy regimens. Copyright © 2012 John Wiley & Sons, Ltd. key words—caffeic acid phenethyl ester (CAPE); antineoplastic; side effect; cancer; treatment INTRODUCTION The most common adverse effects of chemotherapeutic agents such as cisplatin, bleomycine, doxorubucine and the others have extensively been attributed to the reactive oxygen species (ROS), although the mechanism underlying this toxic effects remain unclear. For example, administration of cisplatin causes an increase in lipid peroxidation products and a decrease in the activity of enzymes protecting lipid peroxidation in the kidney. The elimination of these chemotherapeutic-induced toxicity is an ongoing concern. Caffeic acid phenethyl ester (CAPE) has antiinflammatory, immunomodulatory, antiproliferative and antioxidant proper- ties and has been shown to inhibit lipoxygenase activities as well as suppress lipid peroxidation. 1 It is an antiinflammatory component of propolis and reportedly a specific inhibitor of nuclear factor kB (NF-kB). The aim of this review article is to investigate the potential protective role of CAPE on che- motherapeutic-induced and irradiation-induced toxicity in cel- lular systems and animal models. THE GENERAL CHARACTERISTICS OF CAPE CAPE (Figure 1), a polyphenolic component of propolis, has been studied worldwide. It is an active component of propolis and has antitumoural, antiinflammatory, antineo- plastic and antioxidant properties. It is a white powder used as a commercial product with a storage temperature of 20  C and soluble in ethanol, dimethyl sulfoxide (DMSO) and ethyl acetate (50 mg ml 1 ). Its empirical formula is C 17 H 16 O 4 and has 284.31 g mol 1 molecular weight. The pharmacokinetics of CAPE and its catechol-ring fluorinated derivative following intravenous administra- tion to the rats were studied and found that the body clearance values were ranged from 42.1 to 172 ml min 1 kg 1 decreasing with the increasing dose of CAPE. The volume distribution values were ranged from 1555 to 5209 ml kg 1 decreasing with dose, and the elimination half-life was ranged from 21.2 to 26.7 min showing independence from the dose; taken together, CAPE was distributed extensively into the tissues and eliminated rapidly, indicating a high value of volume of distribution and similar short elimination half-life. 2 The in vitro stability of CAPE in rats and human plasma was previ- ously investigated, and CAPE was found to be hydro- lysed to caffeic acid after 6 h within rat plasma in vitro and is also hydrolysed to caffeic acid as the major metabolite in vivo. 3 CAPE is a potent inhibitor of NF-kB. Furthermore, it significantly suppresses the lipoxygenase pathway of arachidonic acid metabolism during inflammation in micromolar concentrations. It completely blocks production of ROS in human neutro- phils and the xanthine/xanthine oxidase (XO) system at 10 mM concentration. *Correpondence to: Dr Omer Akyol, Department of Biochemistry, Hacettepe University Medical Faculty, Sihhiye, Ankara, Turkey. E-mail: oakyol@hacettepe.edu.tr Received 26 December 2011 Revised 26 January 2012 Accepted 6 February 2012 Copyright © 2012 John Wiley & Sons, Ltd. cell biochemistry and function Cell Biochem Funct (2012) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/cbf.2817