Quercetin Down-Regulates Signal Transduction in Human Breast Carcinoma Cells

Abstract

Signal transduction activity was markedly elevated in cancer cells as shown by the increased activity of enzymes utilizing 1-phosphatidylinositol, PI (PI 4-kinase and PI-4-phosphate 5-kinase) for the production of the second messenger inositol 1,4,5-trisphosphate, IP 3, in rat hepatomas (Cancer Res. 54:2611; 5574, 1994) and in human ovarian and breast carcinoma cells (Life Sci. 55:1487, 1994). Quercetin, a flavonoid, in human breast carcinoma MDA-MB-435 cells produced growth inhibition (IC 50 = 55 μM) and cytotoxicity (LC 50 = 26 μM). Quercetin inhibited PI kinase activity in extracts of breast carcinoma cells (IC 50 = 6 μM) and in cultured cells (IC 50 = 10 μM) with a minor inhibition of PIP kinase activity. IP 3 concentration decreased in parallel with PI kinase activity. In time sequence studies quercetin in breast carcinoma cells brought down PI kinase and IP 3 concentration in 60 min to 5 and 6%, respectively; PIP kinase activity was at 63% of controls. The results demonstrate for the first time in proliferating human breast carcinoma cells a reduction by quercetin of the increased capacity for signal transduction, thus providing a novel and sensitive target in cancer cells.