A comparison of vascular-mediated tumor cell death by the necrotizing agents GR63178 and flavone acetic acid.
A vascular component of tumor damage has been identified for the anticancer agent GR63178. The necrotizing activity of this drug and of flavone acetic acid has been compared with their ability to induce growth delay in six murine tumor models. At 24 hr, after a fixed dose of flavone acetic acid (200 mg/kg), all six tumor types appeared 80-100% necrotic histologically, although growth delays ranging from 3 to 79 days were measured. GR63178 (200 mg/kg) induced more variable degrees of necrosis (10 to 95%), but a uniformly small delay in growth (0 to 4 days). These data illustrate that the absence of a tumor-growth response should not be automatically equated with an absence of drug activity. Without assessing tumor response histologically, agents with unusual mechanisms of action may be missed, despite their potential for killing large numbers of tumor cells.
Hill
S A
SA
CRC Gray Laboratory, Mount Vernon Hospital, Northwood, Middlesex, U.K.
Williams
K B
KB
Denekamp
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D005419:Flavonoids / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D007546:Isoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009943:Organophosphorus Compounds
D000970:Antineoplastic Agents; D005419:Flavonoids; D007546:Isoquinolines; D009943:Organophosphorus Compounds; C049328:flavone acetic acid; C072687:fosquidone