α-Tocopheryl Succinate Induces ER Stress, Disruption of Lipid Metabolism, and Apoptosis in a Culture of Normal and Tumor Cells of Epidermal Origin

Abstract: Vitamin E succinate (VES) is a potential antitumor agent known for its targeted effect on the mitochondria of tumor cells. However, data on the proapoptotic mechanism of action of VES are ambiguous, and the effect of VES on normal nontumorigenic cells has not been fully studied. Previously, it was possible to demonstrate the induction of apoptosis by the mitochondrial mechanism under the action of VES on human epidermoid carcinoma A431 cells. The purpose of this work is to investigate the effect of VES on nontumorigenic cells and to identify common mechanisms that are characteristic of both normal and tumor cells, as well as mechanisms that manifest themselves only in one of the categories of cells. To achieve this goal, the effect of VES on such organelles as endoplasmic reticulum (ER) and the Golgi apparatus and the expression of genes associated with ER stress were analyzed, and also the reactive oxygen species (ROS) content and accumulation of lipid droplets in the cytoplasm in human epidermoid carcinoma A431 cells and HaCaT immortalized human keratinocytes were assessed. It was shown that, in cells of both lines, there are signs of ER stress, the content of ROS and lipid inclusions and the number of apoptotic cells increase. At the same time, the key difference between the mechanisms of induction of apoptotic death of A431 and HaCaT cells under the influence of VES lies in the reaction of mitochondria: in A431 cells, apoptotic death is triggered by the mitochondrial mechanism, while HaCaT cells enter apoptosis without the participation of mitochondria. Thus, the targets of VES on normal and tumor cells may differ and, possibly, can complement each other in inducing apoptosis. © Pleiades Publishing, Ltd. 2024. ISSN 1990-519X, Cell and Tissue Biology, 2024, Vol. 18, No. 4, pp. 451–466. Pleiades Publishing, Ltd., 2024.