MetaboLights
An alkyl caffeate ester in which 2-phenylethyl is the alkyl component.
Identification
2-phenylethyl (2E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
2-phenylethyl (2E)-3-(3,4-dihydroxyphenyl)acrylate
2-phenylethyl caffeate
Caffeic acid phenethyl ester
CAPE
Species
Europe PubMed Central results
A Custom Target Next-Generation Sequencing 70-Gene Panel and Replication Study to Identify Genetic Markers of Diabetic Kidney Disease.
Author: Mota-Zamorano S, González LM, Robles NR, Valdivielso JM, Cancho B, López-Gómez J, Gervasini G.
Abstract: Diabetic kidney disease (DKD) has been pointed out as a prominent cause of chronic and end-stage renal disease (ESRD). There is a genetic predisposition to DKD, although clinically relevant loci are yet to be identified. We utilized a custom target next-generation sequencing 70-gene panel to screen a discovery cohort of 150 controls, DKD and DKD-ESRD patients. Relevant SNPs for the susceptibility and clinical evolution of DKD were replicated in an independent validation cohort of 824 controls and patients. A network analysis aiming to assess the impact of variability along specific pathways was also conducted. Forty-eight SNPs displayed significantly different frequencies in the study groups. Of these, 28 with p-values lower than 0.01 were selected for replication. MYH9 rs710181 was inversely associated with the risk of DKD (OR = 0.52 (0.28-0.97), p = 0.033), whilst SOWAHB rs13140552 and CNDP1 rs4891564 were not carried by cases or controls, respectively (p = 0.044 and 0.023). In addition, the RGMA rs1969589 CC genotype was significantly correlated with lower albumin-to-creatinine ratios in the DKD patients (711.8 ± 113.0 vs. 1375.9 ± 474.1 mg/g for TC/TT; mean difference = 823.5 (84.46-1563.0); p = 0.030). No biological pathway stood out as more significantly affected by genetic variability. Our findings reveal new variants that could be useful as biomarkers of DKD onset and/or evolution.
Caffeic acid phenethyl ester attenuates IgE-induced immediate allergic reaction.
Author: Nader MA.
Abstract: Caffeic acid phenethyl ester (CAPE) is the active component of honey bee propolis extracts. The results of the current study demonstrate that CAPE attenuated immunoglobulin (Ig)E-mediated allergic response in mast cells. Oral administration of CAPE inhibited IgE-mediated passive cutaneous anaphylaxis. CAPE effectively reduced both histamine and serotonin (5-HT)-induced vascular permeability in rats. CAPE also reduced histamine and leukotrienes (LTs) release from isolated rat peritoneal mast cells. Moreover, CAPE suppressed contraction induced by histamine (3 × 10(-8)-3 × 10(-5) M), 5-HT (3 × 10(-9)-10(-6) M) and adenosine (3 × 10(-8)-10(-5) M) in guinea pig tracheal zigzag. These findings provide evidence that CAPE may serve as an effective therapeutic agent for allergic diseases.
Caffeic acid phenethyl ester prevents detrimental effects of remote ischemia-reperfusion injury on healing of colonic anastomoses.
Author: Teke Z, Bostanci EB, Yenisey C, Kelten EC, Sacar M, Simsek NG, Duzcan SE, Akoglu M.
Abstract: <h4>Purpose</h4>We aimed to investigate whether caffeic acid phenethyl ester (CAPE) prevents detrimental systemic effects of intestinal ischemia-reperfusion (IR) injury on colonic anastomotic wound healing.<h4>Methods</h4>This experimental study was conducted on 48 male Wistar albino rats. The rats were randomly allocated into four groups and a left colonic anastomosis was performed in all rats: (i) sham-operated group (n = 12), laparatomy without intestinal IR injury; (ii) sham + CAPE group (n = 12), identical to Group 1 except for CAPE treatment (10 μmol/kg, intravenously); (iii) intestinal IR group (n = 12), 60 min of superior mesenteric ischemia followed by reperfusion; and (iv) IR + CAPE-treated group (n = 12) (10 μmol/kg, intravenously, 30 min before the construction of colonic anastomosis). On the postoperative day 7, the rats were subjected to relaparotomy for in vivo measurement of the colonic anastomotic bursting pressure. A colonic segment including the anastomotic site was resected for histopathological evaluation and biochemical analyses. The plasma proinflammatory cytokine levels were measured. Body weight changes were examined.<h4>Results</h4>CAPE treatment significantly increased colonic anastomotic bursting pressures, and colonic anastomotic tissue hydroxyproline contents and antioxidant parameters (p < .05), and significantly decreased oxidative stress markers in colonic anastomotic tissues and plasma proinflammatory cytokine levels (p < .05). Histopathological scores were significantly better due to CAPE administration (p < .05).<h4>Conclusions</h4>This study clearly showed that CAPE treatment prevented the delaying effects of remote IR injury on colonic anastomotic wound healing. Further clinical studies are required to determine whether CAPE has a useful role in the enhancement of gastrointestinal anastomotic wound healing during particular surgeries in which IR-induced organ injury occurs.
The protective role of caffeic acid phenethyl ester against streptomycin ototoxicity.
Author: Bakır S, Özbay M, Gün R, Yorgancılar E, Kınış V, Keleş A, Abakay A, Gökalp O, Topçu İ.
Abstract: <h4>Objective</h4>The aim of this experimental study was to investigate the efficacy of caffeic acid phenethyl ester (CAPE) in the prevention of streptomycin-induced ototoxicity.<h4>Materials and methods</h4>Thirty-two adult Wistar albino rats were divided into 4 groups: control (n = 8), streptomycin (n = 8), CAPE (n = 8), and streptomycin + CAPE (n = 8). Rats were tested with distortion product otoacoustic emissions (DPOAEs) before drug administration. The animals in all groups were killed under general anesthesia on the 45th day following last DPOAE measurements. Hearing results were analyzed statistically to determine differences in amplitudes of DPOAE. Also, the cochleas of each rat were evaluated by histopathological and immunohistochemical examination.<h4>Results</h4>Significant difference was not observed in cochlear hair cells in the control and CAPE groups. In the streptomycin group, severe degeneration of hair cells and increased apoptotic cells were observed. In the streptomycin + CAPE group, although some deteriorations were observed, hair cells were mostly preserved. The DPgram of the streptomycin and streptomycin + CAPE groups was significantly deteriorated (P < .05). The analysis of the DPgram results revealed statistically significant differences between the groups of streptomycin and streptomycin + CAPE (P < .05).<h4>Conclusions</h4>Caffeic acid phenethyl ester treatment attenuated hair cells injury in the inner ear, possibly via its antioxidant effect. Prophylactic administration of CAPE for streptomycin ototoxicity ameliorated hearing deterioration in rats.
Prevention of vancomycin induced nephrotoxicity: a review of preclinical data.
Author: Elyasi S, Khalili H, Hatamkhani S, Dashti-Khavidaki S.
Abstract: <h4>Purpose</h4>Several strategies have been proposed for the prevention of vancomycin-induced nephrotoxicity. Here, we review available evidence supporting the respective strategies.<h4>Method</h4>Data were collected by searching the Scopus, PubMed, and Medline databases and the Cochrane database of systematic reviews. The key words used as search terms were "vancomycin," "nephrotoxicity", "renal failure," "renal damage," "nephroprotective," "renoprotective", and "prevention." Prospective or retrospective observational animal studies that evaluated the effects of a modality for the prevention of vancomycin-induced nephrotoxicity was included.<h4>Results and conclusion</h4>Animal studies show beneficial effects of various antioxidants, such as erdosteine, vitamin E, vitamin C, N-acetylcysteine, caffeic acid phenethyl ester, and erythropoietin, in the prevention of vancomycin-induced nephrotoxicity. However, before these agents can be used in clinical practice, their potential benefits must be confirmed in future randomized controlled human studies.
Suppression of Toll-like receptor 4 activation by caffeic acid phenethyl ester is mediated by interference of LPS binding to MD2.
Author: Kim SY, Koo JE, Seo YJ, Tyagi N, Jeong E, Choi J, Lim KM, Park ZY, Lee JY.
Abstract: <h4>Background and purpose</h4>Toll-like receptors (TLRs) play a crucial role in recognizing invading pathogens and endogenous danger signal to induce immune and inflammatory responses. Since dysregulation of TLRs enhances the risk of immune disorders and chronic inflammatory diseases, modulation of TLR activity by phytochemicals could be useful therapeutically. We investigated the effect of caffeic acid phenethyl ester (CAPE) on TLR-mediated inflammation and the underlying regulatory mechanism.<h4>Experimental approach</h4>Inhibitory effects of CAPE on TLR4 activation were assessed with in vivo murine skin inflammation model and in vitro production of inflammatory mediators in macrophages. In vitro binding assay, cell-based immunoprecipitation study and liquid chromatography-tandem mass spectrometry analysis were performed to determine lipopolysaccharide (LPS) binding to MD2 and to identify the direct binding site of CAPE in MD2.<h4>Key results</h4>Topical application of CAPE attenuated dermal inflammation and oedema induced by intradermal injection of LPS (a TLR4 agonist). CAPE suppressed production of inflammatory mediators and activation of NFκB and interferon-regulatory factor 3 (IRF3) in macrophages stimulated with LPS. CAPE interrupted LPS binding to MD2 through formation of adduct specifically with Cys133 located in hydrophobic pocket of MD2. The inhibitory effect on LPS-induced IRF3 activation by CAPE was not observed when 293T cells were reconstituted with MD2 (C133S) mutant.<h4>Conclusions and implications</h4>Our results show a novel mechanism for anti-inflammatory activity of CAPE to prevent TLR4 activation by interfering with interaction between ligand (LPS) and receptor complex (TLR4/MD2). These further provide beneficial information for the development of therapeutic strategies to prevent chronic inflammatory diseases.
DOI: 10.1111/bph.12091
Caffeic acid phenethyl ester protects against the dopaminergic neuronal loss induced by 6-hydroxydopamine in rats.
Author: Barros Silva R, Santos NA, Martins NM, Ferreira DA, Barbosa F, Oliveira Souza VC, Kinoshita A, Baffa O, Del-Bel E, Del-Bel E, Santos AC.
Abstract: Caffeic acid phenethyl ester (CAPE) is a botanical compound abundant in honeybees' propolis. It has anti-inflammatory, antiviral, antioxidant, immunomodulatory and antitumor properties. Its beneficial effects against neurodegenerative diseases, including Parkinson's disease, have also been suggested and some mechanisms have been proposed. Mitochondrial damage and oxidative stress are critical events in neurodegeneration. Release of cytochrome c from mitochondria to cytosol and the downstream activation of caspase-3 have been suggested as targets of the protective mechanism of CAPE. Most of the studies addressing the protective effect of CAPE have been performed in cell culture. This is the first study to demonstrate the protective effect of CAPE against the dopaminergic neuronal loss induced by 6-hydroxydopamine (6-OHDA) in rats. It also demonstrates, for the first time, the inhibitory effect of CAPE on mitochondrial permeability transition (MPT), a mediator of neuronal death that triggers cytochrome c release and caspase-3 activation. Scavenging of reactive oxygen species (ROS) and metal chelation was demonstrated in the brain-affected areas of the rats treated with 6-OHDA and CAPE. Additionally, we demonstrated that CAPE does not affect brain mitochondrial function. Based on these findings and on its ability to cross the blood-brain barrier, CAPE is a promising compound to treat Parkinson's and other neurodegenerative diseases.
Protective effects of caffeic acid and caffeic acid phenethyl ester against acrolein-induced neurotoxicity in HT22 mouse hippocampal cells.
Author: Huang Y, Jin M, Pi R, Zhang J, Chen M, Ouyang Y, Liu A, Chao X, Liu P, Liu J, Ramassamy C, Qin J.
Abstract: Acrolein-induced oxidative stress is hypothesized to involve in the etiology of Alzheimer's disease (AD). Caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) have antioxidative and neuroprotective properties. The present study investigated the protective effects of CA/CAPE on acrolein-induced oxidative neuronal toxicity. HT22 mouse hippocampal cells were pretreated with CA/CAPE and then exposed to acrolein. Cell viability, intracellular reactive oxygen species (ROS), and glutathione (GSH) level were measured. MAPKs and Akt/GSK3β signaling proteins as well as α/β-secretase of amyloid protein precursor were assayed by Western blotting. Pretreatment with CA/CAPE significantly attenuated acrolein-induced neurotoxicity, ROS accumulation, and GSH depletion. Further study suggested that CA/CAPE showed protective effects against acrolein by modulating MAPKs and Akt/GSK3β signaling pathways. Moreover, CA/CAPE restored the changes of β-secretase (BACE-1) and/or activation of α-secretase (ADAM-10) induced by acrolein. These findings suggest that CA/CAPE may provide a promising approach for the treatment of acrolein-related neurodegenerative diseases, such as AD.
Caffeic acid phenethyl ester as an adjuvant therapy for advanced prostate cancer.
Author: Liu CC, Hsu JM, Kuo LK, Chuu CP.
Abstract: Prostate cancer is the second most frequently diagnosed cancer of men. Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, the majority of prostate cancer patients receiving the androgen ablation therapy will ultimately develop recurrent castration-resistant tumors within 3 years. Chemotherapy shows little effect on prolonging survival for patients with metastatic hormone-refractory prostate cancer. More than 80% of prostate tumors acquire mutation or deletion of tumor suppressor phosphatase and tensin homolog (PTEN), a negative regulator of PI3K/Akt signaling. Caffeic acid phenethyl ester (CAPE) is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment suppresses tumor growth and Akt signaling in human prostate cancer cells. Combined treatments of CAPE with chemotherapeutic drugs exhibit synergistic suppression effects. Pharmacokinetic studies suggest that intraperitoneal injection of CAPE at concentration of 10mg/kg is not toxic. CAPE treatment sensitizes cancer cells to chemotherapy and radiation treatments. In addition, CAPE treatment protects therapy-associated toxicities in animal models. We therefore propose that administration of CAPE is a potential adjuvant therapy for patients with castration-resistant prostate cancer.
Caffeic Acid phenethyl ester as a potential treatment for advanced prostate cancer targeting akt signaling.
Author: Lin HP, Lin CY, Liu CC, Su LC, Huo C, Kuo YY, Tseng JC, Hsu JM, Chen CK, Chuu CP.
Abstract: Prostate cancer is the fifth most common cancer overall in the world. Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, most prostate cancer patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant tumors within 1-3 years after treatment. The median overall survival time is 1-2 years after tumor relapse. Chemotherapy shows little effect on prolonging survival for patients with metastatic hormone-refractory prostate cancer. More than 80% of prostate tumors acquire mutation or deletion of tumor suppressor phosphatase and tensin homolog (PTEN), a negative regulator of PI3K/Akt signaling, indicating that inhibition of PI3K/Akt might be a potential therapy for advanced prostate tumors. Caffeic acid phenethyl ester (CAPE) is a strong antioxidant extracted from honeybee hive propolis. CAPE is a well-known NF-κB inhibitor. CAPE has been used in folk medicine as a potent anti-inflammatory agent. Recent studies indicate that CAPE treatment suppresses tumor growth and Akt signaling in human prostate cancer cells. We discuss the potential of using CAPE as a treatment for patients with advanced prostate cancer targeting Akt signaling pathway in this review article.
DOI: 10.3390/ijms14035264
Caffeic acid phenethyl ester improves burn healing in rats through anti-inflammatory and antioxidant effects.
Author: dos Santos JS, Monte-Alto-Costa A.
Abstract: Although caffeic acid phenethyl ester (CAPE) has beneficial properties, its anti-inflammatory and antioxidant effects on healing burn injury have not been investigated as yet. Female Wistar rats were divided in two groups: burn and burn + CAPE. A scald injury (burn) was performed. CAPE treatment (10 µmol kg) began immediately after the burn and lasted for 14 days. Euthanasia was performed 14 or 70 days after burning. Seven, 21, and 70 days after burning, burn + CAPE group presented smaller wound area. Increase in reepithelialization was observed in burn + CAPE group 28 and 63 days after burning. Fourteen days after wounding, burn + CAPE group presented diminished myeloperoxidase activity and nitrite levels, reduced CD68 and platelet endothelial cell adhesion molecule 1 protein expression, and less oxidative damage (decrease in malondialdehyde (MDA) and carbonyl levels in plasma and lesion extracts). Seventy days after burning, the amount of myofibroblasts and macrophages (CD68 positive) was decreased and the amount of hydroxyproline was increased in burn + CAPE group. Treatment with CAPE improved burn wound healing, showing decrease in inflammatory parameters and in oxidative damage.
Effect of caffeic acid phenethyl ester on intra-abdominal adhesion in rats.
Author: Turgut A, Sak ME, Turkcu G, Ozler A, Soydinc HE, Evsen MS, Evliyaoglu O, Akdemir F.
Abstract: <h4>Background</h4>To determine the impact of caffeic acid phenethyl ester (CAPE) on abdominal adhesion formation after laparotomy.<h4>Methods</h4>Forty female rats were allocated into four distinct groups on which laparotomy alone; laparotomy with traumatization of the uterine horns; laparotomy, traumatization of the uterine horns and intraperitoneal irrigation with saline, and laparotomy, traumatization of the uterine horns and intraperitoneal irrigation with CAPE were performed. After sacrifying the animals on the 14th postoperative day, histopathological examination and biochemical analysis were conducted to evaluate the formation of abdominal adhesions and antioxidant status.<h4>Results</h4>In the CAPE group, total adhesion scores were significantly lower than in the control and saline groups. The CAPE group displayed less inflammation, giant cell formation, fibrosis and fibroblastic activity than the control group. On the other hand, the control group displayed higher total adhesion scores.<h4>Conclusion</h4>The results of this study indicate that the administration of CAPE may have beneficial effects for the prevention of abdominal adhesion formation after laparotomy. Further clinical studies are mandatory to explore the actual therapeutic potential of CAPE.
DOI: 10.1159/000349893
Separation and purification of the antioxidant compounds, caffeic acid phenethyl ester and caffeic acid from mushrooms by molecularly imprinted polymer.
Author: Li N, Ng TB, Wong JH, Qiao JX, Zhang YN, Zhou R, Chen RR, Liu F.
Abstract: Caffeic acid phenethyl ester (CAPE) and caffeic acid (CA), two naturally occurring phenolic antioxidants, have been reported to have a diversity of biological activities. In this investigation, a novel approach to separate and enrich CAPE and CA from 25 species of mushrooms using molecularly imprinted polymers (MIPs) as the sorbent material is reported. The MIPs were synthesized using CAPE as the template, and its adsorption behavior was investigated in detail. In comparison with C18-solid phase extraction (SPE), MIP-SPE displayed high selectivity and good affinity for CAPE and CA. The antioxidant potential of the mushroom extracts, before and after preconcentration using MIPs, was assayed by inhibition of erythrocyte hemolysis and lipid peroxidation. Application of MIPs with a high affinity toward CAPE and CA provides a novel method for obtaining active compounds from natural products.
Ameliorative effects of caffeic acid phenethyl ester on an eccentric exercise-induced skeletal muscle injury by down-regulating NF-κb mediated inflammation.
Author: Shen YC, Yen JC, Liou KT.
Abstract: <h4>Background and purpose</h4>Caffeic acid phenethyl ester (CAPE), a phenolic compound isolated from propolis, displays a variety of biological activities. The aim is to examine the protective effect and mechanisms of CAPE on an eccentric exercise-induced muscle injury model.<h4>Experimental approach</h4>An intermittent downhill eccentric exercise protocol was used. The oxidative tissue injury and expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1), and activation of nuclear factor-κB (NF-κB) were examined. CAPE was applied in a dose of 5 and 10 mg/kg/day, p.o.<h4>Key results</h4>The eccentric exercise induced remarkable skeletal muscle damage uncovered by a dramatic elevation of creatine kinase in the serum and severe degenerative myopathy. These pathophysiological changes were accompanied by an upregulation of the inflammatory responses including protein nitrotyrosylation, poly-ADP-ribose-polymerase (PARP) upregulation, lipid peroxidation as measured by malondialdehyde (MDA) formation, and leukocyte infiltration as measured by myeloperoxidase (MPO). The inflammatory responses primarily resulted from enhanced expression of COX2, iNOS, and production of IL-1β and MCP-1, possibly through activation of NF-κB. All these pathological changes were suppressed by treatment of CAPE.<h4>Conclusions and implications</h4>Our results indicate that CAPE exhibits protective effects against eccentric exercise-induced skeletal muscle damage in rats by blocking the NF-κB-dependent activation of the inflammatory responses.
DOI: 10.1159/000348412
Protective effects of caffeic acid phenethyl ester on dose-dependent intoxication of rats with paraquat.
Author: Silfeler I, Alp H, Ozgur T, Evlioglu O, Celik M, Er M, Yilmaz G.
Abstract: <h4>Purpose</h4>Paraquat (PQ; 1,1'dimethyl-bipyridilium 4,4'-dichloride), which is used extensively throughout the world, is highly toxic to humans. We aimed to investigate the protective effects of different doses of caffeic acid phenethyl ester (CAPE) on PQ-intoxicated rats.<h4>Materials and methods</h4>A total of 80 rats were divided into the following eight groups, comprising 10 rats in each group: group 1: control; group 2: administered with CAPE (10 µmol/kg); group 3: administered with 15 mg/kg PQ (PQ15 group); group 4: administered with 30 mg/kg PQ (PQ30 group); group 5: administered with 45 mg/kg PQ (PQ45 group); group 6: administered with 15 mg/kg PQ + CAPE; group 7: administered with 30 mg/kg PQ + CAPE and group 8: administered with 45 mg/kg PQ + CAPE. Both PQ and CAPE were injected intraperitoneally. Pancreatic tissue was examined with both haematoxylin and eosin and immunochemical staining.<h4>Results</h4>The ratio of the immunohistochemical staining area to the total pancreatic area of the β cells revealed that statistically significant differences were observed only between the PQ and PQ + CAPE groups (p < 0.05).<h4>Discussion</h4>The evaluation of the data suggests that CAPE can be used to prevent acute effects of PQ intoxication.
Caffeic acid phenethyl ester (CAPE), an active component of propolis, inhibits Helicobacter pylori peptide deformylase activity.
Author: Cui K, Lu W, Zhu L, Shen X, Huang J.
Abstract: Helicobacter pylori (H. pylori) is a major causative factor for gastrointestinal illnesses, H. pylori peptide deformylase (HpPDF) catalyzes the removal of formyl group from the N-terminus of nascent polypeptide chains, which is essential for H. pylori survival and is considered as a promising drug target for anti-H. pylori therapy. Propolis, a natural antibiotic from honeybees, is reported to have an inhibitory effect on the growth of H. pylori in vitro. In addition, previous studies suggest that the main active constituents in the propolis are phenolic compounds. Therefore, we evaluated a collection of phenolic compounds derived from propolis for enzyme inhibition against HpPDF. Our study results show that Caffeic acid phenethyl ester (CAPE), one of the main medicinal components of propolis, is a competitive inhibitor against HpPDF, with an IC50 value of 4.02 μM. Furthermore, absorption spectra and crystal structural characterization revealed that different from most well known PDF inhibitors, CAPE block the substrate entrance, preventing substrate from approaching the active site, but CAPE does not have chelate interaction with HpPDF and does not disrupt the metal-dependent catalysis. Our study provides valuable information for understanding the potential anti-H. pylori mechanism of propolis, and CAPE could be served as a lead compound for further anti-H. pylori drug discovery.
Caffeic acid phenethyl ester suppresses proliferation and survival of TW2.6 human oral cancer cells via inhibition of Akt signaling.
Author: Kuo YY, Lin HP, Huo C, Su LC, Yang J, Hsiao PH, Chiang HC, Chung CJ, Wang HD, Chang JY, Chen YW, Chuu CP.
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.
DOI: 10.3390/ijms14058801
In vivo and in vitro antıneoplastic actions of caffeic acid phenethyl ester (CAPE): therapeutic perspectives.
Author: Akyol S, Ozturk G, Ginis Z, Armutcu F, Yigitoglu MR, Akyol O.
Abstract: Cancer prevention and treatment strategies have attracted increasing interest. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, specifically inhibits NF-κB at μM concentrations and shows ability to stop 5-lipoxygenase-catalyzed oxygenation of linoleic acid and arachidonic acid. Previous studies have demonstrated that CAPE exhibits antioxidant, antiinflammatory, antiproliferative, cytostatic, antiviral, antibacterial, antifungal, and, most improtantly, antineoplastic properties. The primary goal of the present review is to summarize and critically evaluate the current knowledge regarding the anticancer effect of CAPE in different cancer types.
Caffeic Acid phenethyl ester inhibits epithelial-mesenchymal transition of human pancreatic cancer cells.
Author: Chen MJ, Shih SC, Wang HY, Lin CC, Liu CY, Wang TE, Chu CH, Chen YJ.
Abstract: Background. This study aimed to investigate the effect of propolis component caffeic acid phenethyl ester (CAPE) on epithelial-mesenchymal transition (EMT) of human pancreatic cancer cells and the molecular mechanisms underlying these effects. Methods. The transforming growth factor β (TGF-β-) induced EMT in human pancreatic PANC-1 cancer cells was characterized by observation of morphology and the expression of E-cadherin and vimentin by western blotting. The migration potential was estimated with wound closure assay. The expression of transcriptional factors was measured by quantitative RT-PCR and immunocytochemistry staining. The orthotopic pancreatic cancer xenograft model was used for in vivo assessment. Results. The overexpression of vimentin was attenuated by CAPE, and the alteration in morphology from polygonal to spindle shape was partially reversed by CAPE. Furthermore, CAPE delayed the TGF-β-stimulated migration potential. CAPE treatment did not reduce the expression levels of Smad 2/3, Snail 1, and Zeb 1 but inhibited the expression of transcriptional factor Twist 2. By using an orthotopic pancreatic cancer model, CAPE suppressed the expression of Twist 2 and growth of PANC-1 xenografts without significant toxicity. Conclusion. CAPE could inhibit the orthotopic growth and EMT of pancreatic cancer PANC-1 cells accompanied by downregulation of vimentin and Twist 2 expression.
DOI: 10.1155/2013/270906
Caffeic acid phenethyl ester inhibits endothelial tissue factor expression.
Author: Gebhard C, Stähli BE, Largiadèr S, Holy EW, Akhmedov A, Camici GG, Lüscher TF, Tanner FC.
Abstract: Caffeic acid phenethyl ester (CAPE) is a component of honeybee hives with various beneficial properties. Tissue factor (TF), the key trigger of thrombosis, is expressed in human endothelial cells. This study was designed to investigate whether CAPE modulates TF expression in human aortic endothelial cells (HAECs). Western blots and real-time polymerase chain reactions were performed. CAPE (10(-7)-10(-5) M) inhibited tumor necrosis factor (TNF)-α induced endothelial TF protein expression by 2.1-fold at 10(-5) M (p<0.0001). Similarly, TF surface activity was reduced (p<0.02). In contrast, TF mRNA expression, TF promoter activity, and mitogen-activated protein (MAP) kinase activation remained unaltered. In conclusion, CAPE inhibits TF protein expression and activity at the posttranscriptional level thereby exhibiting anti-thrombotic potential.
Caffeic acid phenethyl ester, a promising component of propolis with a plethora of biological activities: a review on its anti-inflammatory, neuroprotective, hepatoprotective, and cardioprotective effects.
Author: Tolba MF, Azab SS, Khalifa AE, Abdel-Rahman SZ, Abdel-Naim AB.
Abstract: Caffeic acid phenethyl ester (CAPE) is an important active component of honey bee propolis that possesses a plethora of biological activities. Propolis is used safely in traditional medicine as a dietary supplement for its therapeutic benefits. This review highlights the recently published data about CAPE bioavailability, anti-inflammatory, neuroprotective; hepatoprotective and cardioprotective activities. CAPE showed promising efficacy both in vitro and in vivo studies in animal models with minimum adverse effects. Its effectiveness was demonstrated in multiple target organs. Despite this fact, it has not been yet investigated as a protective agent or a potential therapy in humans. Investigation of CAPE efficacy in clinical trials is strongly encouraged to elucidate its therapeutic benefit for different human diseases after performing full preclinical toxicological studies and gaining more insights into its pharmacokinetics.
DOI: 10.1002/iub.1189
Caffeic acid phenethyl ester inhibits alpha-melanocyte stimulating hormone-induced melanin synthesis through suppressing transactivation activity of microphthalmia-associated transcription factor.
Author: Lee JY, Choi HJ, Chung TW, Kim CH, Jeong HS, Ha KT.
Abstract: Caffeic acid phenethyl ester (1), a natural compound found in various plants and propolis, is a well-known anti-inflammatory, immunomodulatory, and cytotoxic agent. The present study aimed to investigate the molecular events underlying the antimelanogenic activity of 1 in alpha-melanocyte stimulating hormone (α-MSH)-stimulated B16-F10 melanoma cells. In this investigation, 1 effectively reduced α-MSH-stimulated melanin synthesis by suppressing expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2), although this compound did not directly inhibit tyrosinase enzyme activity. On the other hand, the expression and nuclear translocation of microphthalmia-associated transcription factor (MITF) as a key transcription factor for tyrosinase expression regulating melanogenesis were not affected by treatment with 1. The upstream signaling pathways including cAMP response element-binding protein (CREB), glycogen synthase kinase-3β (GSK-3β), and Akt for activation and expression of MITF were also not influenced by 1. Interestingly, 1 inhibited transcriptional activity of a tyrosinase promoter by suppressing the interaction of MITF protein with an M-box containing a CATGTG motif on the tyrosinase promoter. Given the important role of MITF in melanogenesis, suppression of 1 on the function of MITF to transactivate tyrosinase promoter may present a novel therapeutic approach to treat hyperpigmentation disorders.
DOI: 10.1021/np400129z
Caffeic acid phenethyl ester suppresses oxidative stress in 3T3-L1 adipocytes.
Author: Yasui N, Nishiyama E, Juman S, Negishi H, Miki T, Yamori Y, Ikeda K.
Abstract: The generation of oxidative stress, characterized by enhanced reactive oxygen species (ROS) formation, has been found in obesity. ROS production was increased during the differentiation of 3T3-L1 cells into adipocytes. We previously reported that caffeic acid phenethyl ester (CAPE) suppresses 3T3-L1 differentiation to adipocytes through the inhibition of peroxisome proliferator-activated receptor γ. In this study, the preventive effect of CAPE on oxidative stress in 3T3-L1 cells was observed. The results were as follows: (1) ROS production during 3T3-L1 cell differentiation to adipocytes was significantly (p < 0.05) suppressed by CAPE treatment in a concentration-dependent manner, (2) with CAPE treatment, the extracellular superoxide dismutase mRNA expression level significantly increased, but the NOX4 mRNA expression level did not change, and (3) CAPE treatment significantly increased superoxide dismutase (SOD) activity in 3T3-L1 cells. From these results, we suggest that the increased oxidative stress in 3T3-L1 differentiation to adipocytes is attenuated by CAPE treatment. This attenuation may be partly caused by increased SOD production.