IMR Press / EJGO / Volume 21 / Issue 3 / pii/2000155

European Journal of Gynaecological Oncology (EJGO) is published by IMR Press from Volume 40 Issue 1 (2019). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with S.O.G.

Original Research

Signal transduction and biochemical targeting of ovarian carcinoma

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1 Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis, IN, USA
2 Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN, USA
3 Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA
4 Semmelweis Medical University, Budapest, Hungary
5 Meditest Corp., Budapest, Hungary
Eur. J. Gynaecol. Oncol. 2000, 21(3), 231–236;
Published: 10 June 2000
Abstract

The purpose was to identify novel targets for the chemotherapy of ovarian carcinoma. Methods: Assays were worked out to measure the activities of PI kinase, PIP kinase and PLC in ovarian carcinoma samples and in OVCAR-5 cells and to compare the activities to those in normal ovaries. A method was also designed for measuring the con­centration of the end product of signal transduction, IP3. Results and Discussion: Signal transduction activity was markedly increased in ovarian cancer cells as shown by the increasedsteady-state activities of the three enzymes and the elevated concentrations of IP3. Inhibitors blocked activities of PI kinase (quercetin), PIP kinase (genistein), and lowered GTP concentration required for PLC (tiazofurin). Combinations of tiazofurin with quer­cetin, tiazofurin with genistein, and quercetin with genistein yielded a synergistic kill of ovarian cancer cells. Tiazofurin, quercetin and genistein are in various stages of clinical trials. Conclusion: The increased signal transduction activity provides novel, sensitive targets to chemotherapy in ovarian cancer cells.

Keywords
Signal transduction
Ovarian carcinoma
PI kinase
PIP kinase
PLC
IP3
Tiazofurin
Quercetin
Genistein
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