The relationship between tissue levels of flavone acetic acid (NSC 347512) and site dependent anti-tumour activity in murine colon tumours.
Flavone acetic acid (FAA) is extremely active against subcutaneous transplantable tumours in mice, but disappointingly there has been no demonstrable clinical activity. Previous studies have shown that lung tumour deposits are less responsive than the same cells implanted subcutaneously. The aim of this study is to examine the tissue disposition of FAA in an attempt to explain this site-dependent activity. The data show clearly that FAA clearance curves are influenced by the presence of MAC 15A tumours growing either subcutaneously or systemically. The decreased clearance of FAA from MAC 15A tumour bearing animals does not however explain the resistance of lung deposits. Neither can this be explained by differences in metabolism in these different sites. Cytotoxic metabolites have not been detected either in vitro or in vivo and their role in the mechanism of action of FAA is questionable.
Bibby
M C
MC
Clinical Oncology Unit, University of Bradford, UK.
Phillips
R M
RM
Double
J A
JA
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000493:pharmacokinetics* / Q000627:therapeutic use; D066298:In Vitro Techniques; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009368:Neoplasm Transplantation; D010634:Phenobarbital / Q000494:pharmacology; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D005419:Flavonoids; C049328:flavone acetic acid; D010634:Phenobarbital