The mechanism of anticancer action is based on the ability to alkylate especially at the position of guanine

This observation confirms the impact of polyphenols on anti-tumor activities. Jaganathan and Mandal suggested that the polyphenols found in honey, like caffeic acid, caffeic acid phenyl ester, chrysin, galangin, quercetin, kaempferol, acacetin, pinocembrin, pinobanksin and apigenin, may be promising pharmacological agents in the treatment of cancer by reviewing their anti-proliferative and molecular mechanisms. According to Galijatovic et al. some bioactive compounds, such as chrysin, found in honey, have been used to prevent cancer, in a similar fashion as anastrozole, and to treat conditions such as anxiety and inflammation. In our study we observed cytotoxic Z-VAD-FMK Caspase inhibitor activity of H2 in low concentration after 72 h of incubation. This activity may be associated with a high Pb content. Posser et al., 2007 focused, that Pb may cause a series of effect in C6 glioma cells, including activation of p38MAPK and JNK1/2 and a dose-dependent reduction of cell viability. TMZ is an imidazotetrazine derivative used in the therapy of malignant gliomas. Application of TMZ in the management of highgrade glioma is limited by various resistant mechanisms. A recent study showed that TMZ administered together with one of the natural bee product – propolis enhanced the sensitivity of human brain cancer cells, indicating that the combination of TMZ with that natural bee product may be more effective in glioma therapy than using TMZ alone. In our study the stronger reductions of cell viability and DNA synthesis were observed after treatment with combination honey and TMZ than TMZ alone, however higher effect of honey-TMZ combination compared to honey alone was only detected after 48 h of incubation. According to this observations we can only conclude that TMZ does not inhibit the cytotoxic activity of honey. Our and other scientific research has shown that honeys decreased the viability of cells and therefore we decided to study the influence of these natural products on DNA synthesis in U87MG cells. The methyl–thymidine incorporation assay is a widely used, gold standard, method for measuring the inhibition of cell proliferation and has been used successfully to screen and optimize potential new cancer specimens. The results of DNA synthesis after 24, 48, 72 h of exposure to honeys indicate a reduction in U87MG cell proliferation. This fluctuation of DNA synthesis is consistent with the viability of cells in the same time, e.g. the reduction of thymidine incorporation in cells after 72 h is consistent with the reducing of the viability. This observation is also confirmed by a morphological analysis of cells. One of the indicators of the quality of honey is diastase activity. We find a significantly strong negative correlation between this parameter and DNA synthesis after 24 h, 48 h and 72 h of incubation. We found that the intensity of thymidine incorporation depends also on the content of polyphenols in the studied honeys after 24, 48, 72 h treatment of cells. Polyphenols induce DNA damage by affecting the cell cycle phase. The data on the influence of bee honey products on DNA synthesis in glioblastoma cells is poor.