In vitro effects of estradiol, dydrogesterone, tamoxifen and cyclophosphamide on proliferation vs. death in human breast cancer cells.
The effects of 17 beta-estradiol, dihydrodydrogesterone, tamoxifen and cyclophosphamide upon parameters of cell maturation (Mucine1 expression), cell proliferation (Cyclin D1 expression) and apoptosis (loss of nuclear DNA) were studied in estrogen receptor positive (ER+) and negative (ER-) human breast cancer cells. Tamoxifen was the most potent inducer of apoptosis in ER+ and ER- breast cancer cells. 17 beta-estradiol in a concentration of 10(-6) M induced proliferation in ER+ cells after 144 h. incubation, while equimolar co-incubation with dihydrodydrogesterone prevented this effect and even induced a significant increase of cell death. It is speculated that the continuous use of combined 17 beta-estradiol plus dihydrodydrogesterone might be given as hormone replacement therapy without increased risk of breast cancer and even may reduce the relapse rate in breast cancer patients.
Franke
H R
HR
Department of Obstetrics and Gynecology, Medisch Spectrum Twente Hospital Group, PO Box 50000, 7500 KA The, Enschede, Netherlands. hfranke@xs4all.nl
Kole
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Ciftci
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Haanen
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Vermes
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D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D019938:Cyclin D1 / Q000096:biosynthesis / Q000378:metabolism; D003520:Cyclophosphamide / Q000494:pharmacology*; D004394:Dydrogesterone / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009077:Mucins / Q000096:biosynthesis; D045167:Progesterone Congeners / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D009077:Mucins; D045167:Progesterone Congeners; D011960:Receptors, Estrogen; D013629:Tamoxifen; D019938:Cyclin D1; D004958:Estradiol; D003520:Cyclophosphamide; D004394:Dydrogesterone