Abstract
Flavone acetic acid (FAA) is a compound with proven activity against various transplantable colon cancers in mice. In this study it was evaluated against primary colon tumours, chemically induced by methylazoxymethanol in outbred CF1 mice. FAA was given i.v. at doses of 70 or 100 or 150 mg kg-1 every 7 days for 6 weeks. Only 4 out of 60 FAA treated mice died of toxicity. FAA reduced tumour number and tumour burden compared to control mice (P less than 0.05 at least), with no apparent dose-response relationship. Antitumour activity of FAA was comparable to that of 5-fluorouracil (5-FU) used as standard. Moreover, FAA was more effective that 5-FU against large tumours. FAA levels in plasma and different tissues (including colonic neoplastic lesions) after a single i.v. dose of 150 mg kg-1 were investigated. Tumour FAA levels appear insufficient to be responsible for the antitumour activity based only on a direct FAA cytotoxic effect. The results confirm clinical interest in FAA and suggest that mechanisms other than direct cytotoxicity may be involved in its activity.
Highlights
The results confirm clinical interest in Flavone acetic acid (FAA) and suggest that mechanisms other than direct cytotoxicity may be involved in its activity
Summary Flavone acetic acid (FAA) is a compound with proven activity against various transplantable colon cancers in mice. In this study it was evaluated against primary colon tumours, chemically induced by methylazoxymethanol in outbred CF1 mice
4 out of 60 FAA treated mice died of toxicity
Summary
Outbred female CF1 mice, from Charles River Laboratories, USA, were used. They were received when 6-7 weeks old and maintained on chow and water ad libitum, in a controlled environment throughout the study. The experimental model has been described in detail elsewhere (Pratesi & Deschner, 1984). The mice were injected s.c. once a week for 10 weeks with MAM (Janssen Chimica, Belgium), at a dose of 0.4 mg/mouse. After 20 weeks, a few randomly selected mice were killed weekly and their colonic mucosa wa macroscopically inspected for lesions
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