title: The Anticancer Activity of the Old Neuroleptic Phenothiazine-type Drug Thioridazine.
abstract: Thioridazine (TZ), an antipsychotic drug, renders multidrug-resistant (MDR) cancer cells susceptible to cytotoxic agents to which they were initially resistant, has anti-prolilferative activity and apoptosis-inducing properties in various tumor cell lines and cancer stem cells. Whereas the anti-proliferative activity takes place at high concentrations that ensure the intercalation of the compound between nucleic bases (especially rich in G/C bases), much lower concentrations inhibit the export function of the ABCB1 (P-glycoprotein), which is responsible for the MDR phenotype of the cancer cell. The co-administration of TZ with doxorubicin inhibits efflux of doxorubicin and, hence, increases the intracellular concentration of anticancer drug. The (+) and (-) enantiomers of TZ have the same activities as TZ. The main focus of this review is to present extensive evidence provided by our work, confirmed by much later studies, as it supports adjuvant use of TZ with an anticancer drug for MDR cancer therapy.
authors: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary spengler.gabriella@med.u-szeged.hu.
authors: Gabriella
authors: G
authors: Spengler
authors: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors: Ákos
authors: Á
authors: Csonka
authors: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors: Joseph
authors: J
authors: Molnár
authors: Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.|Travel Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal.
authors: Leonard
authors: L
authors: Amaral
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010640:Phenothiazines / Q000627:therapeutic use*; D013881:Thioridazine / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014150:Antipsychotic Agents; D010640:Phenothiazines; C031637:phenothiazine; D013881:Thioridazine
keywords: Phenothiazines; induction of apoptosis; inhibition of P-glycoprotein (ABCB1); inhibition of replication; multidrug-resistant cancer cell lines; resistance to doxorubicin; reversal of multidrug resistance; review; thioridazine; thioridazine derivatives