In Vitro investigation of the effect of theranekron on integrated stress response in SHSY-5Y (neuroblastoma) and l929 (fibroblast) cell lines

Neuroblastoma is a solid tumor originating from the sympathetic nervous system originating from neural crest cells, usually seen in infancy and early childhood. L929 is used as a normal cell line derived from human fibroblasts. It has often been used in studies for the presence of drug-related toxicity. The integrated stress response(ISR) is a signaling pathway that develops against a number of physiological changes and different pathological conditions. There are three different kinases that are used against various conditions in the body such as nutrient deprivation, hypoxia, virus infection, oxidative stress; It is performed with PERK, PKR, GCN-2. Theranekron is an agent prepared from the spider 'Tarantula Cubensis'; it has peptides with neurotoxic effects as well as cell regeneration and hemolytic enzyme inhibitory activities. In this study, for the first time in the literature, potential anti-cancer properties in neuroblastoma and fibroblastic cells were investigated by the application of Theranekron via the integrated stress signaling pathway. The SHSY-5Y and L929 cell lines were duplicated. The dose determination for Theranekron was performed with the MTT test and the IC50 value was determined as 1/10. The effective dose was administered for 24 hours within two cell lines with 90% confluence. Both cell lines were immunohistochemically stained with PERK, PKR, GCN-2 integrated stress markers. He was evaluated with Tunel for apoptosis. Statistically, there were intergroup encounters. Dec. It was found statistically significant that the antibodies used in the SHSY-5Y cancer cell line with Theranekron application increased their immunoreactivity, while this decreased in the cancer cell line that was not applied. From the point of view of L929, it was found statistically significant that these three immunoreactivity decreased in the medicated groups compared to the control L929 without drugs. In the tunnel staining, it was observed that cell death increased especially in the medicated group for the SHSY-5Y neuroblastoma cancer cell line, while cell death was low in the L929 medicated group. In other words, it turned out that theranekron Decin leads to death by increasing integrated stress molecules in cancer, but theranekron has a negligible effect on normal body cells. Accordingly, he highlighted the fact that it can be used as a drug for cancer in certain doses. Given the scarcity of studies on theranekron, we anticipate that our study may be a good reference. Keywords: Apoptosis, Integrated stress response, Cancer, PERK, Theranekron