Oestradiol enhances doxorubicin uptake and cytotoxicity in human breast cancer cells (MCF-7).
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 G0G1-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 microM 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.
Bontenbal
M
M
Division of Endocrine Oncology (Biochemistry and Endocrinology), Rotterdam Cancer Institute, Dr Daniel den Hoed Cancer Center/RRTI, The Netherlands.
Sonneveld
P
P
Foekens
J A
JA
Klijn
J G
JG
D001943:Breast Neoplasms / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism
D004958:Estradiol; D004317:Doxorubicin