Title: Inhibitory Effect of Curcumin on TPA (12-O-Tetradecanoyl Phorbol-13-acetate)- Induced Activation of Protein Kinase C Isoenzyme- Epsilon and c-fos Protein Level in Human Keratinocytes
Abstract:Protein Kinase C (PKC) is a family of isoenzymes that are normally expressed in human keratinocytes. The expression pattern of PKC under induction of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a pot...Protein Kinase C (PKC) is a family of isoenzymes that are normally expressed in human keratinocytes. The expression pattern of PKC under induction of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a potent tumor promoter, is herein reported. Curcumin was evaluated for its effect on TPA-activated PKC-e because PKC-e has been found to have unique oncogenic potential and substrate specificity. Curcumin was shown previously to inhibit TPA-induced AP-1 activity. c-fos protein is inducible by TPA and thus is associated with c-jun to result in an increased AP-1 activity. In the present study the effect of curcumin on TPA-induced c-fos protein level was determined. Human keratinocytes were treated with 160 nM TPA for 1, 2 and 18 h. Upon stimulation by TPA for 1 or 2 h, PKC-α and -e isoenzymes were translocated from cytosol to membrane by 70 or 85 % and they were completely down regulated after treatment for 18 h. However, effects were not found in PKC-δ isoenzyme. Treatment with 20, 40 and 50 µM curcumin inhibited TPA-induced translocation of PKC-e isoenzyme from the cytosol to the membrane in a dose-dependent manner. Curcumin alone did not affect the translocation of PKC-e isoenzyme. The expression level of c-fos protein in human keratinocytes was induced by 160 nM TPA with the maximum result at 2 h, as measured by enhanced chemiluminesence Western blotting detection system. Curcumin pretreated cells decreased TPA-induced c-fos expression in a dose-dependent manner. In conclusion, the induction of c-fos expression and PKC-e activation by TPA occurred in human keratinocytes and this signalling was inhibited by curcumin.Read More
Publication Year: 2005
Publication Date: 2005-01-01
Language: en
Type: article
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Cited By Count: 1
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