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 microM) in particulate extracts from human ovarian carcinoma. In OVCAR-5 cells quercetin produced growth inhibition (IC50 = 63 microM) and cytotoxicity (LC50 = 17 microM). 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 (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.
Prajda
N
N
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46202-5200, USA.
Singhal
R L
RL
Yeh
Y A
YA
Olah
E
E
Look
K Y
KY
Weber
G
G
D019870:1-Phosphatidylinositol 4-Kinase; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D015544:Inositol 1,4,5-Trisphosphate; D011794:Quercetin; D017853:Phosphotransferases (Alcohol Group Acceptor); D019870:1-Phosphatidylinositol 4-Kinase