Evaluation of the effect of topotecan, carvacrol, epigallocatechin gallate and their combination on apoptotic process in neuroblastoma and astrocyte cells

Neuroblastoma is the sympathetic nervous system cancer. It most commonly affects children under 5 years of age and is the most common solid tumor in childhood. Topotecan is a topoisomerase 1 inhibitor. Carvacrol and Epigallocatechin gallate are naturally derived substances with anticancer, antioxidant, and apoptotic properties. The aim of our study was to evaluate the effects of topotecan, carvacrol, EGCG, topotecan+carvacrol, and topotecan+ epigallocatechin gallate combinations on the apoptotic signaling pathway. IC50 values were determined in neuroblastoma and healthy astrocyte cells using the MTT assay. Apoptotic mRNA expressions (topoisomerase 1 and 2, p53, BCL2, BAX, caspase 9, caspase 3, IL1, TNFα) in astrocytes and neuroblastoma cells at the neuroblastoma IC50 dose were analyzed using quantitative real-time PCR. We found that topotecan and carvacrol did not exhibit selective cytotoxic effects between healthy astrocytes and neuroblastoma cells. However, we found that the combination of topotecan+ epigallocatechin gallate and topotecan+carvacrol with epigallocatechin gallate showed selective cytotoxic effects on the neuroblastoma cell line compared to astrocyte cells. The obtained mRNA results can be interpreted as the initiation of apoptosis in neuroblastoma cells in the topotecan, carvacrol, epigallocatechin gallate, and topotecan+epigallocatechin gallate groups. Further studies are needed to investigate this matter in more detail.