ER-positive breast cancer cells

In 2004, Liu et al. made an effort to incorporate estradiol into C-2, 7, and 10 positions in Taxol to target the drug to estrogen receptor (ER) positive breast cancer. For C-2 and C-7 conjugates, no satisfactory results were obtained for either activity or selectivity. But a 7-epi-lO-conjugated taxoid (119) did exhibit some selectivity between ER-positive and negative cancer cells, and ER-(3 (MDA-MB-231 cell) and ER-a expressing (MCF-7) cancer cells. " ... 

The compounds psoralen and isopsoralen were selective ER-a agonists in a HeLa cell assay. These compounds promoted proliferation of estrogen receptor-positive breast cancer cells (MCF-7). Other compounds in psoralea were ER-P agonists (Xin et al. 2010). 

In estrogen receptor (ER)-a-positive breast cancer cells (MCF-7), 100 pg/ml of epimedium (E. brevicomum) inhibited the effects of tamoxifen. ER-a expression in the nucleus was observed with a low dose of epimedium (1 pg/ml), but higher doses (10 or 100 pg/ml) markedly reduced nuclear ER-a protein content (Yap et al. 2007). 

A hydroethanolic extract of hops bound to estrogen receptors in the estrogen receptor (ER)-positive human breast cancer cell line MCF-7. The same extract did not bind to progesterone receptors in the human breast cancer cell line T-47D (Zava et al. 1998). The extract stimulated the proliferation of T-47D (ER positive) cells but had no effect on MDA486 (ER negative) cells (Zava et al. 1998). An extract of hops was shown to have growth-inhibitory activity on estrogen receptor-positive breast cancer cell lines MCF-7 and T-47D (Dixon-Shanies and Shaikh 1999). 

The two major chnical issues are liver failure in children (due to genetic insufficiency) [1802, 1827, 1832, 1833], and neuropathy (in adults), particularly the autosomal recessive disorder spastic paraplegia type 5 [1802, 1815-1818, 1824, 1825], Possible association with Alzheimer s disease has also been reported [1834]. An association with rheumatoid arthritis has been considered [1835], P450 7B1 has also been mentioned regarding (low activity) and the promotion of cell-autonomous ER-positive breast cancer [1836],... 

Brotherick, I., Lennard, T W J., Cook, S., Johnstone, R., Angus, B., Wmthereik, M P, and Shenton, B. K. (1995) Use of the biotinylated antibody Dako-Er ld5 to measure estrogen-receptor on cytokeratm positive cells obtained from primary breast cancer cells Cytometry 20, 74-80. 

Fig. 7.3. Reprinted (in modified form) with permission of John Wiley Sons, Inc. 1995 from Brotherick I, et al (1995). Use of the biotinylated antibody DAKO-ER 1D5 to measure oestrogen receptors on cytokeratin positive cells obtained from primary breast cancer cells. Cytometry 20 74-80.

Toremifene (Fareston , chlorotamoxifen Figure 5.15) has been thoroughly investigated in the laboratory [269-272] and has antitumor activity in carcinogen-induced rat mammary cancer, but is less potent than tamoxifen [272-274]. Toremifene has been tested extensively in phase I—III clinical trials [275-278] and has been approved for use in postmenopausal women with metastatic breast cancer [279]. As predicted from the reduced potency in animal studies, the dose required for activity is 60 mg of toremifene daily (tamoxifen is used at 20 mg daily). The side-effects are similar to those of tamoxifen and, as with tamoxifen, the responses are observed in ER-positive tumors. However, because adjuvant therapy with tamoxifen is standard throughout the world, issues of cross-resistance of tamoxifen and toremifene are important considerations for the use of toremifene in recurrent breast cancer. Laboratory studies by Osborne et al. [280] have demonstrated that toremifene-stimulated tumors can develop from MCF-7 breast cancer cells transplanted into athymic mice. Toremifene is cross-resistant with tamoxifen in tamoxifen-stimulated breast cancer in the laboratory [281]. Similarly, cross-over clinical trials demonstrate that there is little possibility of a second response to toremifene after tamoxifen failure [282, 283]. 

Many in vitro studies using breast cancer cells indicate that phytoestrogens alone imitate the estrogenic effect and induce estrogen-dependent protein (pS2) and cell proliferation in ER-positive MCF-7 cells. " However, in the presence of estrogen, the effect of phytoestrogens was reversed and the effect was not ER dependent. " This issue remains a source of debate. ... 

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