epidermal-growth-factor and caffeic-acid-phenethyl-ester

Epidermal growth factor receptor (EGFR) is upregulated in prostate cancer (PCa). However, suppression of EGFR did not improve the patient outcome, possibly due to the activation of PI3K/Akt signaling in PCa. Compounds able to suppress both PI3K/Akt and EGFR signaling may be effective for treating advanced PCa.. We examined if caffeic acid phenethyl ester (CAPE) simultaneously suppresses the EGFR and Akt signaling, migration and tumor growth in PCa cells.. Wound healing assay, transwell migration assay and xenograft mice model were used to determine the effects of CAPE on migration and proliferation of PCa cells. Western blot, immunoprecipitation, and immunohistochemistry staining were performed to determine the effects of CAPE on EGFR and Akt signaling.. CAPE treatment decreased the gene expression of HRAS, RAF1, AKT2, GSK3A, and EGF and the protein expression of phospho-EGFR (Y845, Y1069, Y1148, Y1173), phospho-FAK, Akt, and ERK1/2 in PCa cells. CAPE treatment inhibited the EGF-induced migration of PCa cells. Combined treatment of CAPE with EGFR inhibitor gefitinib showed additive inhibition on migration and proliferation of PCa cells. Injection of CAPE (15 mg/kg/3 days) for 14 days suppressed the tumor growth of prostate xenografts in nude mice as well as suppressed the levels of Ki67, phospho-EGFR Y845, MMP-9, phospho-Akt S473, phospho-Akt T308, Ras, and Raf-1 in prostate xenografts.. Our study suggested that CAPE can simultaneously suppress the EGFR and Akt signaling in PCa cells and is a potential therapeutic agent for advanced PCa.

Topics: Animals; Caffeic Acids; Cell Line, Tumor; Cell Proliferation; Epidermal Growth Factor; ErbB Receptors; Humans; Male; Mice; Mice, Nude; Phenylethyl Alcohol; Phosphatidylinositol 3-Kinases; Prostate; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt

An experimental study was performed to modify the healing response in caustic esophageal burns to prevent stricture development. Two different agents with different modes of actions, caffeic acid phenethyl ester (CAPE) and epidermal growth factor (EGF), were studied. CAPE has antiinflammatory, immunomodulatory, antioxidant, and antimitotic properties. EGF has known properties in supporting wound healing and in protecting esophagus from injuries.. The model described by Gehanno and its modification by Liu was used to create standard esophageal burns with 50% NaOH. The study was performed with 76 rats in 4 main groups (sham, CAPE, EGF, and control) and 2 subgroups in each for 5 and 28 days of observation. Efficacy of treatment was assessed in 28-day subgroups by measuring weight gain, contrast esophagograms on day 27, histologic evaluation by measuring stenosis index (wall thickness/lumen diameter), and collagen deposition, and biochemically by determining tissue hydroxy proline (OHP) content.. In the end of the study, increase rates of mean body weights of the animals in the 28-day subgroups were as follows: sham, 30%; CAPE, 23%; EGF, 22%; and control, 14%. Although all the animals in subgroups significantly gained weight, the mean weight gain was significantly low in controls when compared with sham, CAPE, and EGF groups (P <.05). Contrast esophagograms on day 27 showed no stenosis in the sham, mild stenosis in CAPE and EGF, and severe stenosis with proximal dilatation in controls. Stenosis indices of the subgroups were as follows: sham, 0.29; CAPE, 0.41; EGF, 0.41; control, 0.84. Index was significantly higher in controls (P <.05). Collagen accumulation scores in the esophageal wall were as follows: Sham, 0.0; CAPE, 0.87; EGF, 0.30; control, 2.70. Scores also were significantly higher in controls (P <.05). Tissue (OHP) levels were as follows (mg/g dry tissue): Sham, 1.48; CAPE, 1.53; EGF, 1.90; control, 4.01. Production of OHP was significantly higher in controls.. The results of the parameters in the study indicate that administration of CAPE and EGF has beneficial effects in the prevention of caustic esophageal strictures. Those effects of CAPE may occur through its antiinflammatory, immunomodulatory, and antioxidant properties, and EGF may occur through its induced proliferative properties on the esophagus.

Topics: Animals; Burns, Chemical; Caffeic Acids; Epidermal Growth Factor; Esophageal Stenosis; NF-kappa B; Phenylethyl Alcohol; Random Allocation; Rats; Rats, Wistar; Wound Healing

Caffeic acid phenethyl ester (CAPE) was evaluated for its potential in regulating keratinocyte proliferation. CAPE inhibited the proliferation of SV40 transformed keratinocytes (Z114) in a concentration- and time-dependent manner. Inhibition by CAPE was seen with 0.5 to 5.0 micrograms/ml at 48 h. Cell toxicity was observed at 10 micrograms/ml by changes in morphology and decreased viability. Pretreatment of Z114 cells with CAPE significantly prevented the full induction of ornithine decarboxylase (ODC) by epidermal growth factor (EGF) in a concentration- and time-dependent manner. Inhibition was observed with a concentration of CAPE as low as 1 microgram/ml, and complete inhibition of ODC induction by EGF occurred at 5 micrograms/ml. Northern analysis showed that treatment of cells with CAPE for 24 h suppressed EGF induction of ODC gene expression. Incubation of Z114 cells with CAPE for 24 h resulted in a concentration-dependent decrease in EGF binding and a 30% reduction in the EGF induced autophosphorylation of the EGF receptor. CAPE decreased both membranous and cytosolic PKC activity in a concentration- and time-dependent manner. Because significant inhibition of keratinocyte proliferation occurred at concentrations of CAPE that interfered with PKC activity and EGF signal transduction but did not cause overt toxicity, CAPE may prove useful for the treatment of hyperproliferative skin diseases.

Topics: Binding Sites; Blotting, Northern; Blotting, Western; Caffeic Acids; Cell Division; Cell Membrane; Cytosol; Dose-Response Relationship, Drug; Epidermal Growth Factor; ErbB Receptors; Humans; Keratinocytes; Male; Ornithine Decarboxylase; Phenylethyl Alcohol; Protein Kinase C; Signal Transduction; Time Factors