LINKAGE OF REDUCTION IN 1-PHOSPHATIDYLINOSITOL 4-KINASE ACTIVITY AND INOSITOL 1,4,5-TRISPHOSPHATE CONCENTRATION IN HUMAN OVARIAN-CARCINOMA CELLS TREATED WITH QUERCETIN

Quercetin inhibited 1-phosphatidylinositol (Pl) 4-kinase, EC 2.7.1.67 (Pl kinase) activity in a concentration-dependent manner (IC50 = 4 mu M) in particulate extracts from human ovarian carcinoma. In OVCAR-5 cells quercetin produced growth inhibition (IC50 = 63 mu M) and cytotoxicity (LC(50) = 17 mu M). The growth inhibition by quercetin was accompanied by an 80% decrease in Pl kinase activity and a 65% decrease in the concentration of the second messenger, inositol 1,4,5-trisphosphate (IP3). When human OVCAR-5 cells were plated and expressed their neoplastic proliferative program in the log phase, Pl kinase and Pl 4-phosphate 5-kinase, EC 2.7.1.68 (PlP kinase) activities coordinately increased to a peak of 5.8- and 4.5-fold, respectively. The results demonstrate for the first time inhibition by quercetin of the enhanced capacity for operation of signal transduction in human ovarian carcinoma cells, thus providing a novel target in cancer cells.