ИСТИНА

In recent time, cancer therapy development has focused on investigating new antitumor agents, such as mitocans. These agents include vitamin E analogues and suppress cancer via apoptosis induction by targeting mitochondria. Also they have various effects on tumor cells, and the whole pattern of action still being poor understood. The purpose of this study was to investigate the effects of α-tocopheryl succinate (α-TOS) on tumor and normal human cell lines derived from stratified epithelium. The action of α-TOS on human epidermoid carcinoma cells A431 and human keratinocytes HaCaT were investigated in this study using live imaging, immunocytochemistry, scanning and transmission electron microscopy, in vitro wound healing model. α-TOS-induced apoptotic cell death in A431 and HaCaT cells was shown to be both dose- and time-dependent, but HaCaT cells were more resistant to the α-TOS-induced apoptosis than A431. In A431 cell line the hyperproduction of reactive oxygen species, changes in size, shape and ultrastructural characteristics of mitochondria followed by the release of cytochrome c from mitochondria to cytosol were observed. These results suggest that in A431 cell line α-TOS induces apoptosis that occurs via the mitochondrial pathway. In HaCaT cells α-TOS did not caused any significant effect on mitochondria. So in this cell line α-TOS-induced apoptosis occurs via non-mitochondrial mechanism. In addition, α-TOS induced sell surface smoothing, actin cytoskeleton reorganization, inhibited wound healing in vitro and caused cell areas decreasing. In A431 cell line these effects occurred in lower concentrations of the agent than in HaCaT cells. Thus, α-TOS selectively induces apoptosis via mitochondrial mechanism in epidermoid carcinoma A431 and, in higher doses, via non-mitochondrial mechanism in non-tumorogenic keratinocytes. It also had various effects on vacuolar system organelles, actin cytoskeleton and cell motility; these effects were similar in both cell lines, but tumor cells were more sensitive to the action of α-TOS. Having multiple targets and exhibiting selectivity for tumor cells, α-TOS can be considered as potential effective drug for tumor therapy.