Toxic effects of tamoxifen on the growth and respiratory activity of Bacillus stearothermophilus

The anticancer drug tamoxifen (TAM) is used as first line therapy in breast cancer. Although tamoxifen is usually considered an estrogen antagonist, s everal studies suggest alternative mechanisms of action. Bacillus stearothe rmophilus has been used as a model to clarify the antiproliferative action of tamoxifen putatively related with drug-membrane interaction. According t o previous data, TAM induces perturbation of membrane structure along with impairment of bacterial growth. The aim of this work was to correlate the e ffects of TAM on growth of intact B. stearothermophilus with the respirator y activity of isolated protoplasts of this bacteria. TAM inhibits bacterial growth and oxygen consumption of protoplasts as a function of concentratio n. Effects on oxygen consumption depend on the substrate used: NADH, allowi ng to study the full respiratory chain and ascorbate-TMPD to probe the fina l oxidase segment. The interaction of TAM with the respiratory components o ccurs at a level preceding the cytochrome oxidase segment. (C) 2001 Elsevie r Science Ltd. All rights reserved.