In vitro antiproliferative effects of tricyclic psychopharmaceutical agents and synergism with some resistance modifiers

Anticancer Res. 1992 Jan-Feb;12(1):273-80.

Abstract

Some of the phenothiazines and dibenz[b,f]azepines exert an antiproliferative effect on HEp-2 and rat prolactinoma cells. The same compounds also have effects on different membrane-bound biochemical events, such as H2O2 formation and the peroxide-generated chemiluminescence of polymorphonuclear leukocytes. The superoxide dismutase inhibition by 7,8-dioxochlorpromazine and 6,9-dioxochlorpromazine have some relation to the growth inhibitory action on the growth of HEP-2 and prolactinoma cells in vitro. The antiproliferative effects of phenothiazines were synergized with resistance modifiers like verapamil, omeprazole and tubulozole-C, due to increased drug-influx or decreased drug-efflux and due to possible action on the cytoskeleton.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Dioxolanes / pharmacology
  • Drug Resistance
  • Drug Synergism
  • Humans
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Phenothiazines / pharmacology*
  • Psychotropic Drugs / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • Superoxide Dismutase / antagonists & inhibitors
  • Tumor Cells, Cultured / drug effects
  • Verapamil / pharmacology

Substances

  • Antineoplastic Agents
  • Dioxolanes
  • Phenothiazines
  • Psychotropic Drugs
  • tubulazole
  • Verapamil
  • Superoxide Dismutase