Pharmacologic and biologic properties of droloxifene, a new antiestrogen.
Pharmacologic investigations with droloxifene in vitro and in vivo revealed that droloxifene is a more efficient antiestrogen than tamoxifen. Droloxifene differs from tamoxifen in the following ways: it has a more than 10-fold higher binding affinity to the estrogen receptor; it shows lower estrogenic and higher antiestrogenic effects on rat uterus, indicating a higher therapeutic index; it more potently inhibits growth of various human ER-positive mammary carcinoma cell lines; short-term exposures with clinically relevant concentrations of droloxifene produce long-term growth inhibition of human ER-positive cancer cells and are more effective than continuous treatment with tamoxifen; it more effectively reduces S-phases and arrests ER-positive cells in G1-phase of the cell cycle; it antagonizes estrogen independent, growth factor stimulated proliferation of MCF-7 cells with higher efficiency; it blocks estrogen activated c-myc expression better than tamoxifen; it more effectively inhibits growth of various experimental tumors of animal (R 3230, DMBA) and human (T61) origin. Therefore, in all experimental systems, it was found that droloxifene is a more potent antiestrogen than tamoxifen.
Eppenberger
U
U
Hormone Laboratory, University Clinics, Basel, Switzerland.
Wosikowski
K
K
Küng
W
W
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D016259:Genes, myc / Q000187:drug effects; D006801:Humans; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011960:Receptors, Estrogen / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; C038345:droloxifene