Biological response of the anti-estrogen ICI 164,384 in human hormone-dependent and hormone-independent mammary cancer cell lines.
The biological response on proliferation and progesterone receptor (PR) of the anti-estrogen ICI 164,384 [N-n-butyl-N-methyl-11-(3,17 beta-dihydroxyestra-1,3,5(10-trien-7 alpha-yl))-undecanamide] was studied in different mammary cancer cell lines. In the hormone-dependent cancer cell lines (MCF-7 and T-47D) this anti-estrogen significantly decreased cell proliferation, but to reduce 50% of the growth in the MCF-7 cells a very low concentration (10(-9) M) is necessary. Similar effects in the T-47D cell are obtained with a dose of 100-1000 times (10(-6)-10(-7) M). The stimulatory effect in cell proliferation induced by estradiol is also inhibited by ICI 164,384 in both cell lines. This anti-estrogen has no effect on proliferation in the anti-estrogen resistant cell line LY-2, or in the hormone-independent cell line MDA-MB-436. Studies on thymidine incorporation correlate with the effect on cell proliferation. ICI 164,384 also blocks the stimulatory effect on progesterone receptor provoked by estradiol in MCF-7 cells and in T-47D cells which contain high concentration levels of progesterone receptor ICI 164,384 significantly decreases the PR concentrations in both the non-treated and estradiol-treated cells. It is concluded that ICI 164,384 is a full antagonist in the hormone-dependent breast cancer cells, but it has no effect in the anti-estrogen-resistant or in hormone-independent cell lines.
Pasqualini
J R
JR
C.N.R.S. Steroid Hormone Research Unit, Foundation for Hormone Research, Paris, France.
Gelly
C
C
D000970:Antineoplastic Agents; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology*; D053284:Polyunsaturated Alkamides; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D011980:Receptors, Progesterone; D004958:Estradiol; C051781:ICI 164384; D013936:Thymidine