Abstract
The cytotoxic effect of doxorubicin on human breast cancer cells (MCF- 7) appeared to be correlated with drug concentration, exposure time and cellular uptake of doxorubicin. The effects of short-term stimulation of the growth of MCF- 7 cells with 30 pM oestradiol was investigated with respect to the uptake of doxorubicin and cell kill. Culture of MCF- 7 cells in steroid hormone-deprived medium resulted in an approx. 90% arrest of the cells in the G0G 1-phase of the cell cycle. Growth stimulation with 30 pM oestradiol caused a 3–5-fold increase in the number of cells in S-G2M phase at between 18 and 24 h after administration of oestradiol to the medium. Incubation of oestradiol-stimulated cells with 0.37 μM doxorubicin during both 1 and 6 h resulted in an augmented inhibition of cell growth compared to unstimulated controls. An enhanced cellular uptake of doxorubicin after administration of oestradiol was observed only after an incubation period of 6 h and not of 1 h. These observations suggest that both an increased sensitivity to doxorubicin and an augmented cellular uptake of the drug may underlie the cytotoxic effects of doxorubicin after pretreatment with oestradiol.
Published Version
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