Effects of tamoxifen on the electron transport chain of isolated rat livermitochondria

Tamoxifen (and 4-hydroxytamoxifen), a nonsteroidal triphenylethylene anties trogenic drug widely used in the treatment of breast cancer, interacts stro ngly with the respiratory chain of isolated rat liver mitochondria. The dru g acts as both an uncoupling agent and a powerful inhibitor of electron tra nsport. Tamoxifen brings about a collapse of the membrane potential. Enzyma tic assays and spectroscopic studies indicate that tamoxifen inhibits elect ron transfer in the respiratory chain at the levels of complex III (ubiquin ol-cytochrome-c reductase) and, to a lesser extent, of complex IV (cytochro me-c oxidase). The activities can be restored by the addition of diphosphat idylglycerol, a phospholipid implicated in the functioning of the respirato ry chain complexes.