Trifluoperazine, an Antipsychotic Drug, Inhibits Viability of Cells Derived From SEGA and Cortical Tubers Cultured In Vitro

This study aimed to identify compounds that inhibit the growth of cells with a hyperactive mTOR pathway, offering potential treatment options for Tuberous Sclerosis Complex (TSC). We obtained cells from subependymal giant cell astrocytoma (SEGA) and cortical tuber (CTuber) tissues of TSC patients to establish SEGA and CTuber cell strains. Focusing on these patient‐derived cell strains, we screened eight compounds from various drug classes for their effects on cell viability in vitro. Five of these compounds demonstrated significant reductions in cell viability and effectively disrupted mTORC1 signaling and autophagy. Trifluoperazine, which exhibited no adverse effects on normal astrocytes, was selected for further study. Combination studies with rapamycin were conducted to evaluate their joint effects on cell viability and autophagy abnormalities, especially in SEGA‐derived cells from rapamycin‐resistant patients. Notably, trifluoperazine showed promising properties by maintaining its efficacy in combination with rapamycin and effectively reducing cell viability, even in rapamycin‐resistant SEGA‐derived cells. Trifluoperazine appears promising as a treatment for TSC. However, further research is crucial to confirm its therapeutic benefits and safety profile in TSC patients, representing a significant direction for future TSC management studies.