AUTHOR:		Chen Z, Gundimeda U, Gopalakrishna R
TITLE:		Ellagic acid induces oxidative inactivation of protein kinase C by modifying both catalytic and regulatory domains (Meeting abstract).
SOURCE:		Proc Annu Meet Am Assoc Cancer Res; 38:A1395 1997   UI: 98638395
ABSTRACT:		Ellagic acid is a polyphenol found in fruits and vegetables, and has been shown to have cancer chemopreventive activity. The mechanism of its antitumor promoting activity is not known. Since protein kinase C (PKC) serves as a receptor for tumor promoters as well as can be oxidatively modified by phenolic compounds, we have determined whether ellagic acid can directly regulate this enzyme. When PKC was preincubated with ellagic acid and then assayed with a low (5 uM) or high (100 uM) concentration of ATP, the enzyme was inhibited with an IC50 of 1 and 4 uM, respectively. Detailed studies revealed that this was due to an irreversible inactivation of the enzyme caused by a redox modification. Ellagic acid-iron complex can inactivate PKC without the need for other metals. Both catalytic and regulatory domains of PKC were modified by ellagic as determined by the loss of kinase activity and phorbol ester binding. But the catalytic domain was 3-fold more sensitive. The thiol agents and vitamin C inhibited this inactivation. In JB6 cells, ellagic acid at low (less than 1 to 5 uM) concentrations induced a modification of PKC which was reversed by an endogenous reduction mechanism, while at higher (5 to 25 uM) concentrations, it induced an irreversible inactivation. Taken together these results suggest that the antitumor promoting action of ellagic acid may be mediated in part by inducing a redox modification of PKC.
LANGUAGE:		ENG
PUBLICATION TYPE:		MEETING ABSTRACTS
TITLE ABBREVIATION:		Proc Annu Meet Am Assoc Cancer Res
YEAR:		1997