ABSTRACT
The polyphenolic compounds present in green tea are preventative against cancer in several animal tumor models. However, direct cytotoxic effects on cancer cells have also been reported. In order to determine whether drinking of green tea has chemopreventive or cytotoxic effects on brain cancer cells, we investigated the effect of the major green tea polyphenol EGCG as a pure substance and as tea extract dietary supplement on primary human glioblastoma cell cultures at the CNS-achievable concentration of 100 nM reported in the literature. We compared this with the effect of the cytotoxic concentration of 500 µM determined to be specific for the investigated primary glioblastoma cultures. After treatment with 500 µM EGCG, strong induction of autophagy and apoptosis was observed. Under treatment with 100 nM EGCG, glioblastoma cells proliferated over the entire observation period of 6 days without any detectable signs of cell death. Only within the first 12 h of treatment was increased accumulation of autophagic vacuoles and increased reactive oxygen species production as a stress response demonstrated. Mild forms of stress, such as treatment with 100 nM EGCG, activate different endogenous repair mechanisms to protect cells. Our data imply that drinking of green tea may have chemopreventive effects, but no direct cytotoxic properties.
Subject(s)
Brain Neoplasms/drug therapy , Catechin/analogs & derivatives , Glioblastoma/drug therapy , Tea/chemistry , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/drug effects , Autophagy/drug effects , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Catechin/administration & dosage , Central Nervous System/drug effects , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Dietary Supplements , Dose-Response Relationship, Drug , Glioblastoma/metabolism , Glioblastoma/pathology , Humans , Lomustine/administration & dosage , Promoter Regions, Genetic , Reactive Oxygen Species/metabolism , Temozolomide/administration & dosage , Tumor Cells, Cultured , Tumor Suppressor Proteins/geneticsABSTRACT
With the increasing use of next-generation sequencing, highly effective targeted therapies have been emerging as treatment options for several cancer types. Recurrent gene-fusions have been recognized in sarcomas; however, options for targeted therapy remain scarce. Here, we describe a case of a sarcoma, associated with a RET::TRIM33-fusion gene with an exceptional response to a neoadjuvant therapy with the selective RET inhibitor selpercatinib. Resected tumor revealed subtotal histopathologic response. This is the first report of successful targeted therapy with selpercatinib in RET-fusion-associated sarcomas. As new targeted therapies are under development, similar treatment options may become available for sarcoma patients.