Tamoxifen stimulates arachidonic acid release from rat liver cells by an estrogen receptor-independent, non-genomic mechanism

BACKGROUND: Tamoxifen is widely prescribed for the treatment of breast cancer. Its success has been attributed to the modulation of the estrogen receptor. I have previously proposed that the release of arachidonic acid from cells may also mediate cancer prevention. METHODS: Rat liver cells were radiolabelled with arachidonic acid. The release of [(3)H] arachidonic acid after various times of incubation of the cells with tamoxifen was measured. RESULTS: Tamoxifen, at micromolar concentrations, stimulates arachidonic acid release. The stimulation is rapid and is not affected by pre-incubation of the cells with actinomycin or the estrogen antagonist ICI-182,780. CONCLUSIONS: The stimulation of AA release by tamoxifen is not mediated by estrogen receptor occupancy and is non-genomic.