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Synergistic
effect of genistein and BCNU on growth inhibition and cytotoxicity of
glioblastoma cells
Khoshyomn
S, Nathan D, Manske GC, Osler TM, Penar PL
Department
of Surgery, University of Vermont College of Medicine, Burlington 05401, USA.
Objective.
Recent experiments have shown that dietary soy isoflavones such as genistein can
significantly suppress invasiveness and growth of a number of human
malignancies.
This study examined whether genistein, at a concentration typical of plasma
levels following soy diet intake, in combination with
1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine) exhibited an additive or
synergistic inhibitory effect on the growth of glioma cells.
Methods.
The human glioblastoma multiforme (GBM) cell line U87 and the rodent C6 glioma
were treated with genistein at 4 microM, combined with BCNU (0-50 microM).
Monolayer cell growth and cytotoxicity, as measured by colonigenic survival in
soft agarose, were then compared in control and drug-treated cultures.
Presence of apoptosis, using the DNA ladder assay and laser scanning cytometry
(LSC), was investigated in all cell lines at those concentrations where an
enhancement of antiproliferative effect of BCNU in presence of genistein was
observed.
Results.
A 32-41% increase in monolayer growth inhibition and a 28-42% increase in colony
cytotoxicity in the U87 cell line were observed when genistein (4 microM) was
added to BCNU in the 0-10 microM dose range.
In the C6 cell line, a 30-36% increase in monolayer growth inhibition and a
39-54% increase in colony cytotoxicity were observed with the BCNU dose range of
0-50 microM.
All experiments showed a significant increase in growth inhibition and a
decrease in colonogenic survival (P < 0.05).
We were unable to detect apoptosis in any of the lines when genistein was
combined with BCNU.
Conclusion.
These results indicate that genistein at typical adult dietary plasma levels can
significantly enhance the antiproliferative and cytotoxic action of BCNU.
The implication for treatment of GBM may be a reduction in the chemotherapeutic
dose recommendations of these agents and subsequently a decrease in the risk of
treatment sequelae for these patients.
PMID: 12125982 [PubMed - in process]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12125982&dopt=Abstract
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