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

Noemi Prajda, Radhey L. Singhal, Y. Albert Yeh, E. Oláh, Katherine Y. Look, George Weber

Research output: Contribution to journalArticle

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Abstract

Quercetin inhibited 1 -phosphatidylinositol (PI) 4-kinase, EC 2.7.1.67 (PI kinase) activity in a concentration-dependent manner (IC50 = 4 μM) in participate extracts from human ovarian carcinoma. In OVCAR-5 cells quercetin produced growth inhibition (IC 50 = 63 μM) and cytotoxicity (LC50 = 17μM). 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 (IP3). 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.

Original languageEnglish
Pages (from-to)1587-1593
Number of pages7
JournalLife Sciences
Volume56
Issue number19
DOIs
Publication statusPublished - Mar 31 1995

Fingerprint

Inositol 1,4,5-Trisphosphate
1-Phosphatidylinositol 4-Kinase
Quercetin
Cells
Carcinoma
Phosphatidylinositols
Phosphotransferases
Signal transduction
Second Messenger Systems
Cytotoxicity
Growth
Inhibitory Concentration 50
Signal Transduction
Neoplasms

Keywords

  • IP
  • ovarian carcinoma
  • PI kinase
  • quercetin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology

Cite this

Linkage of reduction in 1-phosphatidylinositol 4-kinase activity and inositol 1,4,5-trisphosphate concentration in human ovarian carcinoma cells treated with quercetin. / Prajda, Noemi; Singhal, Radhey L.; Yeh, Y. Albert; Oláh, E.; Look, Katherine Y.; Weber, George.

In: Life Sciences, Vol. 56, No. 19, 31.03.1995, p. 1587-1593.

Research output: Contribution to journalArticle

Prajda, Noemi ; Singhal, Radhey L. ; Yeh, Y. Albert ; Oláh, E. ; Look, Katherine Y. ; Weber, George. / Linkage of reduction in 1-phosphatidylinositol 4-kinase activity and inositol 1,4,5-trisphosphate concentration in human ovarian carcinoma cells treated with quercetin. In: Life Sciences. 1995 ; Vol. 56, No. 19. pp. 1587-1593.
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AB - Quercetin inhibited 1 -phosphatidylinositol (PI) 4-kinase, EC 2.7.1.67 (PI kinase) activity in a concentration-dependent manner (IC50 = 4 μM) in participate extracts from human ovarian carcinoma. In OVCAR-5 cells quercetin produced growth inhibition (IC 50 = 63 μM) and cytotoxicity (LC50 = 17μM). 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 (IP3). 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.

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