In vitro methods for screening agents with an indirect mechanism of antitumour activity: xanthenone analogues of flavone acetic acid.
Xanthenone-4-acetic acid (XAA) resembles flavone acetic acid (FAA) in its effects on solid tumours in mice. The activity of methyl-substituted XAA derivatives in vitro was determined using 18 h 51Cr-release assays, continuous exposure growth inhibition assays and stimulation of tumouricidal activity of cultured murine resident peritoneal macrophages. The macrophage assay identified the high biological activity and dose potency of 5-MeXAA in vivo, and was the most accurate in vitro predictor of the ability of congeners to induce either haemorrhagic necrosis of subcutaneous Lewis lung and colon 38 tumours or splenic natural killer activity. In vitro immune stimulation may be more appropriate than direct cytotoxicity for screening compounds with indirect mechanisms of antitumour activity.
Ching
L M
LM
Cancer Research Laboratory, Auckland University School of Medicine, New Zealand.
Finlay
G J
GJ
Joseph
W R
WR
Baguley
B C
BC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014966:Xanthenes / Q000494:pharmacology*; D044004:Xanthones
D000970:Antineoplastic Agents; D014966:Xanthenes; D044004:Xanthones; C066898:5-methylxanthen-9-one-4-acetic acid; C066138:xanthenone-4-acetic acid