In Vitro Investigation of the Effects of Cape Contribution to Chemotherapeutic Drug Treatment on the Neuroblastoma Cell Line (SH SY- 5Y) on the Inflammatory Process

Abstract

Neuroblastoma is a sympathetic nervous system tumor with a 5-year survival rate of less than 50% in high-risk patients that are unresponsive to conventional multimodal treatments. Although chemotherapy, radiotherapy, and surgery are used according to the stages in the treatment protocols, the complications and toxic effects of these treatments are also among the causes that increase mortality. Topotecan is an agent that is actively used in the treatment of neuroblastoma, but its use is limited due to its toxic effects. For these reasons, neuroblastoma is a disease that needs new treatment approaches and agents to reduce the complications of existing treatments. Caffeic Acid Phenethyl Ester (CAPE) is a natural compound that is known for its anti-inflammatory, immunomodulatory, antioxidant, and anticancer properties and is particularly preferred because of its selective effects on cancer cells. Regulation of the inflammatory microenvironment during cancer treatment is an important factor in the treatment plan. According to this information, we aimed to compare the effects of Topotecan and CAPE treatments on the inflammatory process in the SHSY-5Y neuroblastoma cell line with IL-1α, IL-6, IL-18, and VEGF antibodies on the apoptotic process using the TUNEL method. After the cells have been cultured, four groups were formed. Topotecan and CAPE were given separately to the 1st and 2nd groups, Topotecan and CAPE were given together to the 3rd group for 24 hours. A control group was formed by not giving any substance. Then, staining was done with ICC and TUNEL methods. In the results, IL-1α, IL-6, IL-18, and VEGF staining intensities were found to be increased in the CAPE and Topotecan applied groups, especially in the CAPE+Topotecan co-administered group at the end of 24 hours. In the evaluation made with TUNEL staining, although the most apoptotic cells were seen in the CAPE applied group, an increase in apoptosis was also detected in the groups that were administered Topotecan and CAPE+Topotecan together The results of our study showed that CAPE and Topotecan triggered apoptosis by exacerbating inflammation in SH-SY5Y neuroblastoma cells, more apoptotic cells in the CAPE group were more cytotoxic than Topotecan, and when used together, CAPE had a synergistic effect with Topotecan.