Linkage of reduction in 1-phosphatidylinositol 4-kinase activity and inositol 1,4,5-trisphosphate concentration in human ovarian carcinoma cells treated with quercetin.

Abstract Quercetin inhibited 1 -phosphatidylinositol (PI) 4-kinase, EC 2.7.1.67 (PI kinase) activity in a concentration-dependent manner (IC 50 = 4 μ M) in participate extracts from human ovarian carcinoma. In OVCAR-5 cells quercetin produced growth inhibition (IC 50 = 63 μ M) and cytotoxicity (LC 50 = 17 μ M). The growth inhibition by quercetin was accompanied by an 80% decrease in PI kinase activity and a 65% decrease in the concentration of the second messenger, inositol 1,4,5-trisphosphate (IP 3 ). When human OVCAR-5 cells were plated and expressed their neoplastic proliferative program in the log phase, PI kinase and PI 4-phosphate 5-kinase, EC 2.7.1.68 (PIP 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.