Tamoxifen induces accumulation of MCF 7 human mammary carcinoma cells in the G0/G1 phase of the cell cycle

Abstract

When MCF 7 human mammary carcinoma cells in exponential growth phase were treated with tamoxifen a dose-dependent inhibition of cell growth was observed. This inhibition was accompanied by a dose-dependent decrease in the percentage of S phase cells and a concomitant increase in the percentage of cells in the G0/G1 phase of the cell cycle. Simultaneous treatment of cultures with a 10-fold lower concentration of oestradiol completely reversed the growth inhibitory and cell cycle effects of tamoxifen at doses below 5 microM but only partially reversed the effects of higher doses of this drug. It is concluded: (1) that tamoxifen-induced growth inhibition is associated with major changes in the cell cycle kinetic parameters of MCF 7 cells, indicating that this drug is a cell cycle phase-specific growth inhibitory agent and (2) that not all the anti-proliferative and cell cycle effects of tamoxifen in vitro are reversed by simultaneous treatment with oestradiol. This suggests that tamoxifen, in addition to having effects on cell proliferation that are reversed by oestrogens and are likely to be oestrogen receptor-mediated, has antitumor activity in vitro that involves biochemical mechanisms independent of the oestrogen receptor system.