Chemotherapeutic Effect of SR9009, a REV-ERB Agonist, on the Human Glioblastoma T98G Cells

WAGNER, PAULA M.; MONJES, NATALIA M.; GUIDO, MARIO E.

ASN Neuro

SAGE Publications Inc.

Lugar: T Oaks, CA; Año: 2019 vol. 11

lioblastoma multiforme is the most aggressive brain tumor, and human T98G cells constitute a useful glioblastoma multiforme model to evaluate the chemotherapeutic agents. Modern life (shiftwork, jetlag, etc.) may cause circadian disorganization promoting higher cancer risk and metabolic disorders. Although little is known about the tumor-intrinsic circadian clock function, pharmacological modulation of circadian components may offer selective anticancer strategies. REV-ERBs are heme-binding circadian clock components acting as repressors of processes involved in tumorigenesis such as metabolism, proliferation, and inflammation. A synthetic pyrrole derivative (SR9009) that acts as REV-ERBs-specific agonists exhibits potent in vivo activity on metabolism and tumor cell viability. Here, we investigated SR9009 effects on T98G cell viability, differential chemotherapy time responses, and underlying metabolic processes (reactive oxygen species [ROS] and lipid droplets [LDs]) and compared it