ИСТИНА

Stable cell–cell contacts and cell polarity are essential for functionality of epithelial tissues. Carcinoma cells often acquire morphological and functional characteristics of mesenchymal cells due to the loss of baso-apical polarity, reorganization of cytoskeleton and adhesion junctions, a process known as epithelial– mesenchymal transition (EMT). The molecular changes in EMT include down-regulation of epithelial markers, such as E-cadherin, alpha-catenin and keratins, as well as increased expression of mesenchymal proteins N-cadherin, Snail, vimentin. We investigated the influence of mitochondria-targeted antioxidant SkQ1 on cervical cancer cells. SkQ1 treatment caused reorganization of beta-cytoplasmic actin and adhesion junctions in the SiHa and Ca-Ski cancer cells. E-cadherin and alpha-catenin in the SiHa cells were upregulated after incubation with SkQ1. Increase of the tumor suppressor E-cadherin was probably caused by Snail down-regulation after SkQ1 treatment. In Ca-Ski cells incubation with SkQ1 decreased mesenchymal markers N- cadherin and vimentin, but didn’t influence E-cadherin and Snail, which is much less abundant in Ca-Ski than in SiHa. SkQ1 suppressed proliferation of the SiHa cells but didn’t influence proliferation of non-malignant epithelial HaCaT cells. Mitogen-activated protein kinases (MAPK) are signaling molecules that control proliferation, motility, adhesion and survival. We investigated the involvement of MAPK signaling pathways in the morphology and biochemistry changes of cervical cancer cells, induced by SkQ1. We identified that SkQ1 treatment decreased ERK1/2 kinase activation in the SiHa and Ca-Ski cells. Mitochondria-targeted antioxidant SkQ1 initiated changes in the cell shape, cytoskeleton and intercellular contacts organization, epithelial and mesenchymal markers profile and MAPK signaling, thus SkQ1 reverted EMT and partially restored the differentiated epithelial phenotype in both types of cervical cancer cells.