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

Area of Science:

• Neuro-oncology
• Pharmacology
• Cell Biology

Background:

• Tuberous Sclerosis Complex (TSC) is a genetic disorder characterized by hyperactive mTOR pathway signaling.
• This hyperactivity leads to the development of benign tumors, including subependymal giant cell astrocytomas (SEGA) and cortical tubers (CTuber).
• Current treatments for TSC-associated tumors have limitations, necessitating the exploration of novel therapeutic agents.

Purpose of the Study:

• To identify novel compounds that inhibit the growth of TSC-associated cells with a hyperactive mTOR pathway.
• To evaluate the efficacy of these compounds in patient-derived cell lines.
• To investigate the potential of trifluoperazine as a therapeutic agent for TSC, including its combination with rapamycin.

Main Methods:

• Establishment of SEGA and CTuber cell strains from patient tissues.
• In vitro screening of eight compounds for effects on cell viability.
• Assessment of compound effects on mTORC1 signaling and autophagy.
• Combination studies of trifluoperazine with rapamycin in SEGA-derived cells.

Main Results:

• Five of the screened compounds significantly reduced cell viability and disrupted mTORC1 signaling and autophagy.
• Trifluoperazine demonstrated efficacy without adverse effects on normal astrocytes.
• Trifluoperazine maintained efficacy in combination with rapamycin, even in rapamycin-resistant SEGA cells.
• Trifluoperazine effectively reduced cell viability in rapamycin-resistant TSC cells.

Conclusions:

• Trifluoperazine shows promise as a potential treatment for Tuberous Sclerosis Complex.
• The compound is effective in reducing cell viability and inhibiting mTORC1 signaling in patient-derived TSC cells.
• Further clinical research is required to validate the therapeutic benefits and safety of trifluoperazine for TSC patients.