The Anticancer Activity of the Old Neuroleptic Phenothiazine-type Drug Thioridazine

Area of Science:

• Pharmacology
• Oncology
• Biochemistry

Background:

• Multidrug resistance (MDR) in cancer limits the effectiveness of chemotherapy.
• P-glycoprotein (P-gp) is a key efflux pump responsible for the MDR phenotype.
• Thioridazine (TZ) is an antipsychotic drug with potential anticancer properties.

Purpose of the Study:

• To review evidence supporting the adjuvant use of Thioridazine (TZ) in treating MDR cancer.
• To highlight TZ's mechanisms in overcoming cancer cell resistance.

Main Methods:

• Review of existing research, including the authors' own work.
• Analysis of TZ's effects on cancer cell lines and cancer stem cells.
• Investigation of TZ's interaction with nucleic acids and P-gp.

Main Results:

• TZ exhibits anti-proliferative and apoptosis-inducing effects on various cancer cells.
• At lower concentrations, TZ inhibits P-gp, reversing MDR.
• Co-administration of TZ with doxorubicin increases intracellular drug concentration.

Conclusions:

• Thioridazine (TZ) demonstrates significant potential as an adjuvant therapy for MDR cancer.
• Evidence supports the use of TZ to enhance the efficacy of conventional anticancer drugs.