THE ANTIPROLIFERATIVE PROPERTIES OF 4-BENZYLPHENOXY ETHANAMINE DERIVATIVES ARE MEDIATED BY THE ANTIESTROGEN BINDING-SITE (ABS), WHEREAS THE ANTIESTROGENIC EFFECTS OF TRIFLUOPROMAZINE ARE NOT

被引:14
作者
POIROT, M
GARNIER, M
BAYARD, F
RIVIERE, I
TRAORE, M
WILSON, M
FARGIN, A
FAYE, JC
机构
[1] CHU RANGUEIL,ENDOCR EXP LAB,INSERM,U168,F-31054 TOULOUSE,FRANCE
[2] UNIV TOULOUSE 3,CHIM BIOORGAN LAB,F-31062 TOULOUSE,FRANCE
关键词
D O I
10.1016/0006-2952(90)90539-W
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We compared the anti-proliferative properties of 4-benzylphenoxy-N ethyl morpholine (mor-pho-BPE) and trifluopromazine (TFP) on both the human breast cancer cell lines, MCF7, and its tamoxifen-resistant variant RTx6. We found that the calmodulin antagonist trifluopromazine (TFP) which bound ABS weakly, inhibited MCF7 cell growth but did not follow the relationship observed for diphenylmethane derivatives between MCF7-inhibitory potencies and their Ki. Regarding the tamoxifenresistant RTx6 cells, TFP but not morpho-BPE induced inhibition of the proliferation. Using a tritiated derivative of morpho-BPE, two distinct binding sites could be demonstrated. Indeed, a low affinity binding site was present in both cell lines whereas a high affinity binding site was mainly found in MCF7 cells although being in lower concentration (<10%) in rtx6 cells. Both tamoxifen and TFP displaced morpho-BPE from the two binding sites. The uptake and efflux of the tritiated drug were similar in the two cell lines. The drug did not appear to be metabolized. We concluded that TFP and morpho-BPE belong to distinct classes of molecules and that ABS mediates the anti-proliferative action of diphenylmethane derivatives but not the inhibitory effect of the calmodulin antagonist TFP. © 1990.
引用
收藏
页码:425 / 429
页数:5
相关论文
共 19 条
  • [1] CYTOPLASMIC AND NUCLEAR ESTRADIOL AND PROGESTERONE RECEPTORS IN HUMAN ENDOMETRIUM
    BAYARD, F
    DAMILANO, S
    ROBEL, P
    BAULIEU, EE
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1978, 46 (04) : 635 - 648
  • [2] A DIPHENYLMETHANE DERIVATIVE SPECIFIC FOR THE ANTIESTROGEN BINDING-SITE FOUND IN RAT-LIVER MICROSOMES
    BRANDES, LJ
    HERMONAT, MW
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 123 (02) : 724 - 728
  • [3] Dixon M., 1964, ENZYMES, P328
  • [4] FURTHER EVIDENCE FOR A BIOLOGICAL ROLE OF ANTI-ESTROGEN-BINDING SITES IN MEDIATING THE GROWTH INHIBITORY-ACTION OF DIPHENYLMETHANE DERIVATIVES
    FARGIN, A
    BAYARD, F
    FAYE, JC
    TRAORE, M
    POIROT, M
    KLAEBE, A
    PERIE, JJ
    [J]. CHEMICO-BIOLOGICAL INTERACTIONS, 1988, 66 (1-2) : 101 - 109
  • [5] SOLUBILIZATION OF A TAMOXIFEN-BINDING PROTEIN - ASSESSMENT OF ITS MOLECULAR MASS
    FARGIN, A
    FAYE, JC
    LEMAIRE, M
    BAYARD, F
    POTIER, M
    BEAUREGARD, G
    [J]. BIOCHEMICAL JOURNAL, 1988, 256 (01) : 229 - 236
  • [6] FAYE JC, 1983, P NATL ACAD SCI-BIOL, V80, P3158, DOI 10.1073/pnas.80.11.3158
  • [7] ANTI-ESTROGEN SPECIFIC, HIGH-AFFINITY SATURABLE BINDING-SITES IN RAT UTERINE CYTOSOL
    FAYE, JC
    LASSERRE, B
    BAYARD, F
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1980, 93 (04) : 1225 - 1231
  • [8] ANTIESTROGENS, DIFFERENT SITES OF ACTION THAN THE ESTROGEN-RECEPTOR
    FAYE, JC
    FARGIN, A
    VALETTE, A
    BAYARD, F
    [J]. HORMONE RESEARCH, 1987, 28 (2-4) : 202 - 211
  • [9] GULINO A, 1986, CANCER RES, V46, P6274
  • [10] JORDAN VC, 1984, PHARMACOL REV, V36, P245