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Synergistic
action of quercetin and genistein in human ovarian carcinoma cells
Shen F, Weber
G
Laboratory for
Experimental Oncology, Indiana University School of Medicine, Indianapolis
46202-5119, USA
Ovarian carcinoma is the fourth most common cause of cancer death in women and
there has been a steady increase in the age-adjusted cancer death rates in the
past 25 years in the US.
However, patients who become cisplatin resistant
respond poorly to available cytotoxic agents; therefore, discovering novel
targets for ovarian carcinoma is vital.
Quercetin, an anticancer agent, arrests
the cell cycle at G1 and S phase boundary.
Genistein, a plant flavonoid, attacks
the cell cycle at G2 and/or early M phases in most carcinoma cells.
Quercetin
and genistein block the phosphatidylinositol conversion to IP3 signal
transduction pathway mainly by inhibiting 1-phosphatidylinositol 4-kinase (PI
kinase, EC 2.7.1.67) and 1-phosphatidylinositol 4-phosphate 5-kinase (PIP kinase,
EC 2.7.1.68), respectively.
Because each drug attacks a different phase of the
cell cycle and reduces IP3 concentration by attacking different signal
transduction enzymes, we tested the hypothesis that the two drugs might be
synergistic in human carcinoma cells.
In human ovarian carcinoma OVCAR-5 cells
in growth inhibition assay, the IC50S for quercetin and genistein were (mean +/-
SE) 66 +/- 3.0 and 32 +/- 2.5 microM; in clonogenic assays they were 15 +/- 1.2
and 5 +/- 0.5 microM, respectively. When quercetin was added to the cultures of
OVCAR-5 cells followed 8 h later by genistein, synergism was observed in growth
inhibition and clonogenic assays.
The synergistic action of quercetin and
genistein may be of interest in clinical treatment of human ovarian carcinoma.
PMID: 9563007 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9563007&dopt=Abstract
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