Currently available anticancer therapies are inadequate and spur demand for improved technologies. Among others, the utilization of nanocarriers for anticancer drug delivery has shown great potential in cancer treatment. Nanocarriers can improve the therapeutic efficiency of the drugs with minimization of the undesirable side effects. To evaluate potential application of this technology, two forms of nanocarriers have been studied: multi-walled carbon nanotubes (MWCNTs) and apoferritin. The aim of this study was to determine, whether given cytostatics (ellipticine, etoposide and doxorubicin) are bound to these nanotransporters and how are they released from them, especially depending on pH. Since the pH of the tumor cells is lower than the pH of healthy cells it would be preferred that the drugs would release from nanocarriers at the lower pH while at the physiological pH the release of the drug would be eliminated. The results found show that ellipticine is actually released from its MWCNT- and apoferrtin-encapsulated form at acidic pH (5.0), while at pH 7.4 its interaction with nanocarriers is stable. Ellipticine released from MWCNT is activated by microsomal enzymes to reactive metabolites (13- hydroxyellipticine and 12-hydroxyellipticine) forming DNA adducts. The results indicate that both...

Cancer cells are able to adapt to different stress factors such as hypoxia, which is caused by insufficient tumor vascularization. An increased acetylation status of histones H3 and H4 in UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines was found to be a mechanism of adaptation of these cells to hypoxia. An increase in acetylation of histones H3 and H4 is suggested to cause changes in the structure of chromatin that lead to activation of gene transcription. In addition, cultivation of tested neuroblastoma cells under hypoxic conditions changes expression of proteins of a transcription factor N-myc, which is essential for development of neuroblastomas. This transcription factor is also responsible for a metabolic adaptation of neuroblastoma cells, increases their aggressiveness and its expression leads to a worse prognosis of the disease. Inhibitors of histone deacetylases (HDAC) are suggested to be the promising agents exhibiting various anticancer effects. They can induce cell cycle arrest, differentiation or programmed cell death in sensitive tumors. In this study, the effect of one of inhibitors of HDACs, valproate, on expression of proteins of transcription factors N-myc and hypoxia inducible factor 1α (HIF-1α) was investigated. Valproate decreases protein levels of both transcription factors in...