Synergistic down-regulation of signal transduction and cytotoxicity by tiazofurin and quercetin in human ovarian carcinoma cells

Fei Shen, Maria Herenyiova, George Weber

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Ovarian carcinoma is one of the most common causes of cancer death in women. Tiazofurin, a C-nucleoside, arrests the cell cycle at S phase and reduces the activities of PI (phosphatidylinositol) utilizing enzymes in signal transduction by depleting cellular GTP concentration. Quercetin (QN), a flavonoid, attacks the cell cycle at the G1 and S phase boundary and mainly inhibits PI kinase (1-phosphatidylinositol 4-kinase, EC 2.7.1.67) activity in the signal transduction pathway. Because tiazofurin and QN attack different biochemical targets and arrest different phases of the cell cycle, we tested the hypothesis that the two drugs might be synergistic against human carcinoma cells. In human ovarian carcinoma OVCAR-5 cells in growth inhibition assay, the IC50s (drug concentration that inhibits 50% of cell proliferation) for tiazofurin and QN were (mean ± SE) 13 ± 1.2 and 66 ± 3.0 μM; in elonogenic assays they were 6 ± 0.5 and 15 ± 1.2 μM, respectively. When tiazofurin was added to cells followed 12 h later by QN, synergism was observed in both growth inhibition and clonogenic assays. The combination also yielded synergistic reduction of IP3 (inositol 1,4,5- trisphosphate) concentration in the cells which may explain, at least in part, the synergistic action of tiazofurin and QN in OVCAR-5 cells. The protocols yielding synergism may have implications in the clinical treatment of human ovarian carcinoma.

Original languageEnglish
Pages (from-to)1869-1876
Number of pages8
JournalLife Sciences
Volume64
Issue number21
DOIs
StatePublished - Apr 16 1999

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tiazofurin
Signal transduction
Quercetin
Cytotoxicity
Signal Transduction
Down-Regulation
Cells
Carcinoma
Assays
Phosphatidylinositols
S Phase
Cell Cycle
Inositol 1,4,5-Trisphosphate
1-Phosphatidylinositol 4-Kinase
Cell proliferation
G1 Phase
Phase boundaries
Growth
Guanosine Triphosphate
Cell Cycle Checkpoints

Keywords

  • IP concentration
  • Ovarian carcinoma
  • Quercetin
  • Signal transduction
  • Tiazofurin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Synergistic down-regulation of signal transduction and cytotoxicity by tiazofurin and quercetin in human ovarian carcinoma cells. / Shen, Fei; Herenyiova, Maria; Weber, George.

In: Life Sciences, Vol. 64, No. 21, 16.04.1999, p. 1869-1876.

Research output: Contribution to journalArticle

Shen, Fei ; Herenyiova, Maria ; Weber, George. / Synergistic down-regulation of signal transduction and cytotoxicity by tiazofurin and quercetin in human ovarian carcinoma cells. In: Life Sciences. 1999 ; Vol. 64, No. 21. pp. 1869-1876.
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