Thio-disaccharides are composed of two monosaccharides linked by sulfur at position 1-4. The replacement of an oxygen atom by a sulfur atom produce new carbohydrates with different physico-chemical character and the biological activity. The sulfur atom is the functional group that render these compounds therapeutically useful as we confirmed that certain thiodisacharides exhibit anticancer properties.[1, 2] The aim of this work was to investigate mechanism of their anticancer action in human cervix adenocarcinoma HeLa cell line and we were also focused on oxidative stress analysis. The selected (1-4)-S-thiodisaccharides (FCP6, 7 and 9) as depicted in Scheme 1. The complete oxidative stress analysis included genotoxicity using a comet assay and DNA repair enzymes, flow cytometry analysis of apoptosis and mitochondrial function. The analysis of the cellular reactive oxygen species (ROS) level and generation of ROS by a studied compound with a free-radical nitrone spin trap was performed. FCP6, FCP7 and FCP9 induced oxidative DNA lesions in cancer cell line and level of cellular ROS. ROS induced by FCPs are not of mitochondrial origin – thio-disaccharides did not disturb their function. ROS arose from metabolic conversions of FCP because the level of oxidatively modified bases in DNA was higher in cells incubated at 37°C to those incubated at 4°C. Specifically, Tocopherol, which was used as a spin trap, decreased the level of oxidative DNA lesions induced by FCPs. We noticed that the effects were stronger in cells incubated with FCP6 as compared with those incubated with FCP7 and FCP9. In conclusion – thio-disaccharides exhibit an anticancer potential as they evoke oxidative stress and oxidative DNA damage in cancer cells. The mechanism of ROS induction by thio-sugars in cancer cells still needs to be evaluated. 1. A potential CARB-pharmacophore for antineoplastic activity 1. Witczak ZJ, Poplawski T, Czubatka A, Sarnik J, Tokarz P, VanWert AL, Bielski R. Bioorg Med Chem Lett. 2014, 24(7), 1752-7. 2. Thio-sugar motif of functional CARB-pharmacophore for antineoplastic activity. 2. Witczak ZJ, Sarnik J, Czubatka A, Forma E, Poplawski T. Bioorg Med Chem Lett. 2014, 24(24), 5606-11. Acknowledgment This work was supported by The Polish National Science Centre, decision nr DEC-2011/01/B/NZ4/03391 and DEC-2014/15/N/NZ7/02948

Thio-disaccharides induces an oxidative stress that kills cervix epitheloid carcinoma cells

251st National Meeting (2016)

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