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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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BIOLOGICAL
EFFECTS OF WATER-SOLUBLE FULLERENE DERIVATIVE - IN VITRO STUDIES
ON HUMAN TUMOR CELLS LINES
D.
Jakimov1, G. Bogdanović1,
V. Kojić1, S. Turšijan1,
L. Aleksić1, M. Baltić1,
A. Đorđević2,
M. Vojinović-Miloradov2
1Experimental
Oncology Department and Laboratory for Immunobiology, Institute
of Oncology Sremska Kamenica, Sremska Kamenica, Yugoslavia
2Department of Chemistry, Faculty of Science,
University of Novi Sad, Novi Sad, Yugoslavia
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ABSTRACT
Fullerenes
represent a class of sphere-shaped molecules made exclusively of
carbon atoms. The chemical modification of fullerene [C60] molecule
toward water-soluble derivatives resulted in compounds exhibiting
a variety of biological activities. Several in vitro and in vivo
studies have shown that fullerols, polyhydroxylated [C60] fullerene
derivatives, are free radical scavengers and potent antioxidative
agents in biological system, which can explain their antiproliferative
and enzyme inhibition activity.The aim of this paper was to investigate
activity of fullerol C60(OH)24 at nanomolar concentrations, on growth
and proliferation of human tumor cell lines and its modulatory effect
on Adriamycin (ADR), Cisplatin (cis-Pt) , Taxol, and Thiazofurine
- induced cytotoxicity in selected human tumor cell lines. Human
erythroleukemia K562 cell line and human breast adenocarcinoma cell
lines- MCF7 and MDA-MB-231, were used in the study.The following
methods were used: incorporation of radiolabeled thymidine for a
DNA synthesis; flow cytometry for cellular DNA content and cell
cycle distribution; SRB assay for cell growth and cytotoxicity of
antitimor drugs.Capability of K562 cells to synthesize a DNA, their
mitotic activity and cell cycle distribution has been evaluated
3, 24 and 48 hours after fullerol treatment. No significant differences
were found in morphological appearance between control and fullerol
treated cells analyzed by light microscopy. A mitotic index of fullerol
treated cells was decreased in comparison to control regardless
of the period of cell incubation with fullerol. Synthesis of DNA
of fullerol treated K562 cells was inhibited, but only at the highest
fullerol concentration. The cell cycle distribution pattern of K562
cells treated with fullerol at nanomolar concentration was comparable
to that of the control but increasing number of cells in G2M phase
was observed during the treatment period.Combination of fullerol
and cytostatics, given simultaneously, resulted in various growth
inhibition patterns, depending on fullerol concentration, type of
antitumor drug and cell line as well.Fullerol C60(OH)24 differently
modulated cytotoxic effects of given cytostatics - protective efffect
was more pronounced against drugs whose action is based on formation
of free radicals.The results showed that C60(OH)24 induced a cytostatic
rather than a cytotoxic activity and also modulated cell cycle of
the K562 cells influencing both synthetic and mitotic cell cycle
phase.Modulation of Adriamycin, cis-platinum, or Tiazofurin-induced
cytotoxicity by fullerol can be explained by its antioxidative activity
while in Taxol-induced cytotoxicity inhibition might be mediated
by other mechanism e.g. effect on cytoskeleton.The results are in
accordance with our previous data relating to growth-inhibitory
activity of the fullerol against selected human tumor cell lines.
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Keywords:
Fullerene; Cell line; Cell cycle; DNA synthesis; Mitosis; Cytotoxicity;
Antitumor drug |
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