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8th
International Inter University Scientific Meeting
Academy of Studenica
NEW
TRENDS IN DIAGNOSTICS AND THERAPY OF MALIGNANT TUMORS
Organizer:
Institute of Oncology Sremska Kamenica, Yugoslavia
Co-organizers: Institute
for Oncology and Radiology, Belgrade, Yugoslavia;
"Aristotel School", Thessaloniki, Greece
President: Prof.Dr.
Vladimir Vit. Baltić
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SYNERGISTIC
EFFECTS OF SULFINOSINE AND 8-CL-CAMP ON HUMAN GLIOMA AND NEUROBLASTOMA
CELL LINES
D.
Janković, M. Pešić, J. Šaponjić, V. Pejanović, S. Kanazir, Lj.
Rakić, S. Ruzdijić
Institute for Biological Research "Sinisa
Stankovic", Department of Neurobiology and Immunology, Laboratory
of Molecular Neurobiology, Beograd, Yugoslavia
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ABSTRACT
Compounds
that could block tumor proliferation and induce tumor cell differentiation
in malignant gliomas and neuroblastomas could represent a valuable
tool in anti-cancer treatment. 8-Cl-cAMP is a cAMP analogue, currently
in Phase II clinical trials, that displays growth inhibition and
differentiation in a broad spectrum of human cancer cell lines,
without causing citotoxicity. In our study, we combined 8-Cl-cAMP
and sulfinosine, a purine ribonucleoside, that has the ability for
binding glutathione and decreasing its concentration in target cells,
therefore inhibiting the actions of glutathione-S-transferase and
glutathione-peroxidase. Consequently, the cellular detoxification
is aggravated and cells become susceptible for the action of other
drug. The antiproliferative effect of 8-Cl-cAMP and sulfinosine
was examined on human glioma (U87 MG) and neuroblastoma (SK-N-SH)
cells in vitro by using BrdU cell proliferation ELISA assay, based
on BrdU incorporation during DNA synthesis. Trypan blue dye exclusion
test was preformed for determination of 8-Cl-cAMP and sulfinosine
cytotoxicity.Antiproliferative effect of sulfinosine, examined in
BrdU cell proliferation ELISA assay, was not profound (with IC50
values: 16.2 µM for U87 MG and 41.5 µM
for SK-N-SH). 8-Cl-cAMP has shown better effect on both cell lines
with IC50 values: 2.5 µM
for U87 MG and 8.2 µM
for SK-N-SH. U87 MG cells were simultaneously treated with low concentrations
of SF (2.5, 5 and 10 µM)
and 8-Cl-cAMP (0.5, 1 and 1.5 µM).
Although, these concentrations in single treatment have not shown
antiproliferative effect on glioma cells, 8-Cl-cAMP has decreased
IC50 value for SF 2 times with 0.5 µM,
as well as 3.4 times with 1 µM
and 5 times with 1.5 µM.
SK-N-SH cells were also simultaneously treated with SF (2.5, 5 and
10 µM)
and 8-Cl-cAMP (2, 4 and 6 µM).
The similar trend was observed in neuroblastoma cells: 8-Cl-cAMP
has decreased IC50 value for SF 4.5 times with 2 µM,
as well as 5.3 times with 4 µM
and 6.5 times with 6 µM.
Cell viability assessed with trypan blue dye exclusion assay was
about 95% for both glioma and neuroblastoma even with the highest
concentrations of 8-Cl-cAMP and sulfinosine, indicating that these
substances were not cytotoxic under these experimental conditions.These
results indicate strong synergism of combined SF and 8-Cl-cAMP action
and could be a new design for a future therapy of glioma and neuroblastoma.
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Keywords:
Glioma: Neuroblastoma: 8-Cl-cAMP: Sulfinosine: Drug combinations:
Antiproliferative effects |
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