Signal transduction and biochemical targeting of ovarian carcinoma.
The purpose was to identify novel targets for the chemotherapy of ovarian carcinoma.


METHODS
Assays were worked out to measure the activities of P1 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.


CONCLUSIONS
Signal transduction activity was markedly increased in ovarian cancer cells as shown by the increased steady-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.


CONCLUSIONS
The increased signal transduction activity provides novel, sensitive targets to chemotherapy in ovarian cancer cells.
Weber
G
G
Indiana University School of Medicine, Indianapolis 46202-5119, USA.
Shen
D F
DF
Li
W
W
Yang
H
H
Look
K Y
KY
Abonyi
M
M
Prajda
N
N
D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D012254:Ribavirin / Q000031:analogs & derivatives / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
D012254:Ribavirin; D011794:Quercetin; D019833:Genistein; C033706:tiazofurin