Further evidence for a biological role of anti-estrogen-binding sites in mediating the growth inhibitory action of diphenylmethane derivatives.
Several diphenylmethane derivatives have been synthesized with variable affinities for Anti-estrogen Binding Sites (ABS) but not for the estrogen receptor. Using these molecules as probes it is shown that their binding affinities for ABS correlate with their abilities to inhibit the growth of MCF-7 human breast cancer cells. In contrast they have no influence on the proliferation of tamoxifen-resistant variant cells (RTx6) in which ABS are undetectable. These data support the conclusion that ABS has a functional role in the anti-proliferative effect of triphenylethylene anti-estrogens and structurally related compounds.
Fargin
A
A
INSERM U 168, Departement d'Endocrinologie, Chu Rangueil, Toulouse, France.
Bayard
F
F
Faye
J C
JC
Traore
M
M
Poirot
M
M
Klaebe
A
A
Perie
J J
JJ
D001559:Benzhydryl Compounds; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011955:Receptors, Drug; D011960:Receptors, Estrogen / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001559:Benzhydryl Compounds; D004965:Estrogen Antagonists; D011955:Receptors, Drug; D011960:Receptors, Estrogen; D004958:Estradiol; C010129:diphenylmethane