Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 100
Potential cytoprotective effects of new synthesised sulphur containing compounds
Tzvetomira A. Tzanova1, 3, Ognyan Petrov2, Laurent Brault3, Denyse Bagrel3,
Margarita H. Karaivanova1
1. Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str, 1000 Sofia,
Bulgaria; e-mail: tzvete_tzanova@abv.bg
2. Faculty of Chemistry, University of Sofia"St. Kliment Ohriski", 1 James
Bourchier Blvd, Sofia 1164, Bulgaria; e-mail: OPetrov@chem.uni-sofia.bg
3. Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, UFR
SciFA, Université Paul Verlaine - Metz, Campus Bridoux, rue du Général Delestraint,
57070 Metz, France; e-mail: bagrel@univ-metz.fr
Cancer pathogenic mechanisms are associated with DNA damage, oxidative stress, and
chronic inflammation. Therapies goal to maximizing tumour death while minimizing damage
to normal tissues. The delivery of high doses of chemotherapy will increase survival though it
is often limited by the development of severe adverse effects. Numerous studies have
demonstrated that sulphur-containing nucleophiles can antagonize the dose–limiting effects of
alkylating agents. The aim of this study is to assess the chemoprotective potential of seven
new 1-(4-Bromo-2-mercaptophenyl)-3, 4-dimethyl-1, 3-dihydroimidazol-2-one derivatives.
The chemoprotective effect of these synthesized sulphur-containing compounds was
evaluated on HL-60, HL-60/Dox, SKW-3, K-562, EJ and MCF-7 malignant cell lines (MTT
assay). Four of the tested molecules present an interesting effect since they did not display
cytotoxic effects on cells at concentrations up to 100 µM when used as pre-treatment. They
limit the cell mortality induced by cisplatin on MCF-7 breast carcinoma cell line. As expected
cisplatin treatments resulted in accumulation of cells in S phase. Two compounds, containing
mercaptoacetyl group, did not influence cisplatin effect on the cell cycle (DNA
quantification) indicating that these molecules did not seem to interact directly with cisplatin.
According to these results the oxidative stress was evaluated. A pre-treatment of the cells with
these compounds followed by administration of cisplatin did not affect the level of GSH, the
major intracellular antioxidant (HPLC method). As reactive oxygen species are important
mediators of antineoplastic drugs, we actually focus on the evaluation of antiradical and
antioxidant activities of the most interesting compounds as well as on their implication in
apoptosis induction.
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