Synergistic anticancer action of reversibly and irreversibly acting ligands of poly (ADP-ribose) polymerase.
The synergistic interaction of two ligands (INH2BP and the prodrug INO2BA) of PARP I has been demonstrated for two human leukemia cell lines (855-2 and HL-60), for a human lung cancer cell (A549) and for Eras 20 cancer cells. Synergism was calculated using kinetic combination constants based on cell multiplication rates. Reducing cellular GSH content by BSO strongly augmented synergism, an effect partly explained by the removal of C-NO scavenging (by GSH). However, INH2BP action was augmented by BSO, an effect most probably explained by the sensitization of the cell to apoptosis by GSH removal.
Kun
Ernest
E
Department of Anatomy, School of Medicine, University of California, San Francisco Medical Center, San Francisco, CA 94143-0452, USA. ernestkun@mac.com
Kirsten
Eva
E
Mendeleyev
Jerome
J
D000970:Antineoplastic Agents / Q000378:metabolism*; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008024:Ligands; D011065:Poly(ADP-ribose) Polymerases; D005978:Glutathione