The anticancer activity of the old neuroleptic phenothiazine-type drug thioridazine

Gabriella Spengler, Ákos Csonka, Joseph Molnár, Leonard Amaral

Research output: Contribution to journalReview article

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5701-5706
Number of pages6
JournalAnticancer research
Volume36
Issue number11
DOIs
Publication statusPublished - Nov 2016

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Keywords

  • Induction of apoptosis
  • Inhibition of P-glycoprotein (ABCB1)
  • Inhibition of replication
  • Multidrug-resistant cancer cell lines
  • Phenothiazines
  • Resistance to doxorubicin
  • Reversal of multidrug resistance
  • Review
  • Thioridazine
  • Thioridazine derivatives

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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