Influence of different combinations of tamoxifen and toremifene on estrogen receptor-positive breast cancer cell lines.
Acquired tamoxifen (TAM) resistance is supposed to be the major cause of hormone therapy failure in estrogen receptor (ER)-positive breast cancer patients. Toremifene (TOR), a chlorinated TAM-related compound, has been found to be more effective and less toxic than TAM. Moreover 4-hydroxy-toremifene (OH-TOR), like 4-hydroxy-tamoxifen (OH-TAM), is the most effective metabolite in human. To better understand the relative role of TAM, TOR, OH-TAM, and OH-TOR, singly or in combination, we studied their effect on MCF7, ZR-75.1, and T47D cell lines, which, despite their positive receptor status, have a different responsiveness to estradiol and antiestrogenic compounds. The results may be summarized as follows; in MCF7 cells, all compounds, singly or in association, showed an inhibitory effect; ZR75.1 cells were resistance to TAM and OH-TAM, but partially sensitive to TOR and OH-TOR; in T47D cells, all compounds displayed their estrogenic activity and induced cell growth. These result suggest the inefficacy of these triphenylethylene derivatives as a hormone treatment even when given in a simultaneous or sequential combination.
Coradini
D
D
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italia.
Biffi
A
A
Cappelletti
V
V
Di Fronzo
G
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004965:Estrogen Antagonists / Q000008:administration & dosage; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage; D017312:Toremifene / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; D017312:Toremifene