Antiproliferative Effects Of Tamoxifen Research Articles

Treatment of endometrial adenomatosis with tamoxifen

1. Treatment with tamoxifen of persistent endometrial hyperplasia with adenomatous phenomena resistant to traditional hormone therapy caused disappearance of adenomatosis in 90.5% cases after 3 months. 2. The character of the menstrual cycle during therapy may serve as a clinical prognostic criterion of its effectiveness. 3. The antiproliferative effect of tamoxifen may be manifest not only at the target cell level but also by increasing the synthesis of SSBG and reducing the free fractions of sex steroids.

Recombinant interferon-α2b affects proliferation, steroid receptors and sensitivity to tamoxifen of cultured breast cancer cells (CG-5)

Exposure of CG-5 human breast cancer cells to recombinant interferon (IFN)-alpha 2b results in a significative inhibition of cell proliferation; this is observed when cells are cultured in their standard conditions and is not modified if serum concentration present in the culture medium is lowered. Estrogen receptors are increased in CG-5 cells following a 5 day treatment with concentrations of IFN-alpha 2b ranging from 10 to 1000 IU/ml of culture medium. Progesterone receptors seem to be more influenced by a longer treatment with the drug (7 days). The Kd of both receptors is not modified by the exposure of cells to IFN-alpha 2b. Finally, the antiproliferative effect of tamoxifen on CG-5 cells is amplified by the simultaneous addition to culture medium of IFN-alpha 2b even at very low concentrations.

Interaction of antiestrogens with binding sites for muscarinic cholinergic drugs and calcium channel blockers in cell membranes

The interaction of tamoxifen and clomifene with membrane binding sites for the cholinergic ligand quinuclidinyl benzilate (QNB) and the dihydropyridine calcium antagonist nitrendipine was studied. Both tamoxifen and clomifene competed with [3H]-QNB and [3H]-nitrendipine for their binding to the receptor in the membrane fractions from the urinary bladder and myometrium. The extent of inhibition as judged by the Ki values for both antiestrogens was similar at both receptor sites. The data suggest that the antiproliferative effects of tamoxifen may involve not only the intracellular estrogen-receptor system but also receptors for neurotransmitters and membrane calcium channels.

Human recombinant interferon α increases oestrogen receptor expression in ZR-75-1 human breast cancer cells and sensitizes them to the anti-proliferative effects of tamoxifen

Human recombinant interferon α increases oestrogen receptor expression in ZR-75-1 human breast cancer cells and sensitizes them to the anti-proliferative effects of tamoxifen

Growth patterns and hormonal sensitivity of primary tumor, abdominal metastasis and ascitic fluid from human epithelial ovarian carcinomas in the tumor colony-forming assay.

The human tumor colony forming assay was used to evaluate the response of ovarian carcinoma cells from primary tumors, ascitic fluids and metastasis to hormonal treatment. In 12/35 patients a sufficient colony formation (greater than 30 colonies/dish) was obtained in order to perform a simultaneous drug testing. The plating efficiency of the metastatic samples (0.12%) was significantly higher (P less than 0.053) than those from the primary tumor (0.076%) or those that were derived from the ascitic fluid (0.082%). Colonies from the metastatic tissues could be evaluated 2-4 days earlier than those from primary tumors. These discrepancies may be due to a heterogeneity in the clonable tumor cell compartment of primary tumor and metastasis. The antiproliferative properties of the antiestrogen tamoxifen and the progestin gestoneron were studied. In 9/12 cases a significant, dose-dependent reduction of colony formation (greater than 70-90% of the controls) was observed after continuous exposure to 1 mumole tamoxifen. No correlation between the dose response and the content of steroid receptors was found. Even estrogen receptor negative tumor samples showed a maximal antiproliferative effect of tamoxifen.

New evidence that the antiestrogen binding site may be a novel growth-promoting histamine receptor (?H 3) which mediates the antiestrogenic and antiproliferative effects of tamoxifen

Using as a probe [3H]-DPPE (N,N-diethyl-2-[(4-phenylmethyl)phenoxy]ethanamine HCl), a novel compound selective for the antiestrogen binding site (AEBS), new evidence is presented that this site could be a growth-promoting histamine receptor of a type not previously described (?H3). In the rat uterus, DPPE alone at a concentration of 4 mg/kg acts as an estrogen antagonist, unlike TAM alone which is a partial estrogen agonist. In the presence of exogenous estradiol, both TAM and DPPE are partial antagonists. This suggests that the "antiestrogenic" effects of tamoxifen are mediated through AEBS/?H3 while the estrogenic effects are mediated through ER.

The antiproliferative effect of tamoxifen in breast cancer cells: mediation by the estrogen receptor

The effects of tamoxifen (Tam) and its 4-hydroxylated metabolite (OH-Tam) on the growth of two human breast cancer cell lines (MCF7 and BT20) were evaluated by fluorometric DNA assay. The effects of the antiestrogens were dependent upon their concentrations and the nature of the cells. At concentrations below 4 μM, the degree of inhibition was related to their relative affinities for the estrogen receptor and was totally reversed by estradiol in MCF7 cells. No inhibition was observed in the estrogen receptor negative cell line BT20. This supports and extends the idea that the antiproliferative effect of Tam at these concentrations is mediated by the estrogen receptor even in the absence of measurable estradiol concentration. At concentrations greater than 4 μM, Tam was cytotoxic on MCF 7 and BT20 mammary cell lines within 2 days of treatment. The cytotoxic effect was irreversible and was not prevented by occupation of the estrogen receptor with estradiol, suggesting that it was not mediated by the estrogen receptor. The cytotoxicity of the triphenylethylene drugs, however, has some specificity since it was not observed in a fibroblast rat cell line (49F) or in the two mammary cell lines with similar high concentrations of estradiol and diethylstilbestrol.