The potential usage of caffeic acid phenethyl ester (CAPE) against chemotherapy-induced and radiotherapy-induced toxicity

Department of Biochemistry, Fatih University Medical School, Ankara, Turkey.
Cell Biochemistry and Function (Impact Factor: 2.01). 07/2012; 30(5):438-43. DOI: 10.1002/cbf.2817
Source: PubMed


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 κB 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.

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    • "Takino and Mochida (1982) reported that the biological activity of propolis is mainly due to the presence of the flavonoid content. Recently, Akyol et al. (2012) stated that caffeic acid phenethyl ester (CAPE), which is the major compound that is extracted from the propolis, has antiinflammatory , antiproliferative, antioxidant, cytostatic, antiviral , antibacterial, antifungal, and antineoplastic properties. It has been reported also that CAPE can regulate antioxidant enzymes, inhibit lipid peroxidation, and reduce hepatic damage (Ates et al., 2006; Bhadauria et al., 2007). "
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    ABSTRACT: Abstract Context: Cyclophosphamide (CTX) is a common anticancer agent used for the treatment of several malignancies. However, upon treatment, it induces severe toxicity due to its oxidative stress capability. Propolis, a natural product collected by honey bees, has shown several biological activities, such as free radical scavenging and antioxidant agent. Objective: This study elucidates the protective effects of propolis against CTX-induced changes in mice. Materials and methods: Forty-eight male Swiss albino mice were divided into four groups; group 1 was intraperitoneally (i.p.) injected with 200 µL of phosphate buffer saline (PBS), group 2 was injected with 100 mg/kg/d propolis, group 3 was injected with a single dose of CTX (200 mg/kg), and group 4 was injected with a single dose of CTX (200 mg/kg) followed by propolis (100 mg/kg) for 7 consecutive days. After 12 d, mice were bled and then sacrificed to analyze the hematological, biochemical, and histological parameters. Results: The results indicated that CTX-injected mice showed an increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine and a decrease in the total number of white blood cells (WBCs) and platelets. Moreover, dramatically changes in the histological architectures of the liver and kidney were observed. The mice that were injected with CTX/propolis showed an improvement in the levels of ALT, AST, urea, creatinine, WBCs, and platelets. Moreover, the histological picture of the liver and kidney was significantly improved. Conclusions: In conclusion, propolis might be considered an effective agent in ameliorating the toxicity resulted from CTX treatment.
    Pharmaceutical Biology 10/2014; 53(2):1-7. DOI:10.3109/13880209.2014.914230 · 1.24 Impact Factor
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    • "It has been suggested to be also an effective antioxidant [21]. CAPE might be even used as a protective agent against chemotherapy-induced and radiotherapy-induced toxicity [17]. "
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    ABSTRACT: Background: Whereas oxidative reactions occur in all tissues and organs, the thyroid constitutes such an organ, in which oxidative processes are indispensable for physiological functions. In turn, numerous metabolic reactions occurring in the liver create favourable conditions for huge oxidative stress. Melatonin is a well-known antioxidant with protective effects against oxidative damage perfectly documented in many tissues, the thyroid and the liver included. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, has been suggested to be also an effective antioxidant. The aim of the study was to evaluate the effects of CAPE on Fenton reaction-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) in porcine thyroid and liver, and to compare the results with protective effects of melatonin. Methods: Thyroid and liver homogenates were incubated in the presence of CAPE (500; 100; 50; 10; 5.0; 1.0 μM) or melatonin (500; 100; 50; 10; 5.0; 1.0 μM), without or with addition of FeSO4 (30 μM) + H2O2 (0.5 mM). The level of lipid peroxidation was measured spectrophotometrically and expressed as the amount of MDA + 4-HDA (nmol) per mg of protein. Results: Whereas CAPE decreased the basal LPO in a concentration-dependent manner in both tissues, melatonin did not change the basal LPO level. When antioxidants were used together with Fenton reaction substrates, they prevented - in a concentration-dependent manner and to a similar extent - experimentally-induced LPO in both tissues. Conclusions: Protective antioxidative effects of CAPE in the thyroid and the liver are similar to those caused by melatonin. CAPE constitutes a promising agent in terms of its application in experimental and, possibly, clinical studies.
    Thyroid Research 06/2014; 7(1):5. DOI:10.1186/1756-6614-7-5
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    • "Previously, CAPE treatments have been shown to sensitize cancer cells to chemotherapeutic drugs and radiation treatment by inhibiting pathways that lead to treatment resistance in animal models [46]. CAPE treatments have also been shown to protect tissues and organs from chemotherapy-associated toxicities in animal models [14,15,46–54]. Therefore, oral cancer patients receiving chemotherapies may benefit from co-treatment of CAPE, which may enhance the regression of tumors and protect tissues and organs of patients from chemotherapy. "
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    ABSTRACT: Caffeic acid phenethyl ester (CAPE) is a bioactive component extracted from honeybee hive propolis. Our observations indicated that CAPE treatment suppressed cell proliferation and colony formation of TW2.6 human oral squamous cell carcinoma (OSCC) cells dose-dependently. CAPE treatment decreased G1 phase cell population, increased G2/M phase cell population, and induced apoptosis in TW2.6 cells. Treatment with CAPE decreased protein abundance of Akt, Akt1, Akt2, Akt3, phospho-Akt Ser473, phospho-Akt Thr 308, GSK3β, FOXO1, FOXO3a, phospho-FOXO1 Thr24, phospho-FoxO3a Thr32, NF-κB, phospho-NF-κB Ser536, Rb, phospho-Rb Ser807/811, Skp2, and cyclin D1, but increased cell cycle inhibitor p27Kip. Overexpression of Akt1 or Akt2 in TW2.6 cells rescued growth inhibition caused by CAPE treatment. Co-treating TW2.6 cells with CAPE and 5-fluorouracil, a commonly used chemotherapeutic drug for oral cancers, exhibited additive cell proliferation inhibition. Our study suggested that administration of CAPE is a potential adjuvant therapy for patients with OSCC oral cancer.
    International Journal of Molecular Sciences 05/2013; 14(5):8801-17. DOI:10.3390/ijms14058801 · 2.86 Impact Factor
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