Flavone 8-acetic acid: our current understanding of its mechanism of action in solid tumours

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Abstract
Flavone 8-acetic acid (FAA) represents a novel chemical structure undergoing clinical trials as an anticancer drug. Its unusual properties tend to distinguish it from a conventional cytotoxic compound, particularly in the response of solid murine tumours; as a consequence, novel mechanisms of action are currently under investigation. In this review we summarised these mechanisms into one of the three categories (a) direct cytotoxicity, (b) biologic response modifier and (c) pharmacologic effector and considered the evidence for and against each. FAA is cytotoxic to tumour cells in vitro, but only at high concentrations and after long exposures. In vivo it is considerably more cytotoxic to the same cells, and it is unlikely that direct cytotoxicity alone can account for this difference. FAA stimulates NK cell activity, induces interferon α and synergises with interleukin 2 in the treatment of murine renal cancer. However, a definite link between immunomodulation and antitumour activity has still to be confirmed. Perhaps FAA's most unusual property is its ability to reduce tumour blood flow dramatically, which may provide the appropriate conditions for reactive chemistry to occur. Finally, a combination of the above mechanisms probably work together in producing the drug's unique spectrum of antitumour activity.