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Abstract
We report evidence indicating that the isoflavone genistein induces a dose-dependent antiproliferative effect in the human uterine adenocarcinoma cell lines HEC-1A, HEC-1B, AN3 CA and RL95-2. Cell growth inhibition resulted from a partial G2/M block and from the appearance of a hypodiploid DNA peak (reduction in nuclear DNA content), suggestive of apoptosis. In HEC-1A cells, we found that both cell cycle impairment and the appearance of a hypodiploid DNA peak were time-dependent, triggered by similar concentrations of the isoflavone and not affected by the presence of serum in the culture medium. However, while the genistein-induced cell cycle'arrest was fully reversible, the appearance of the hypodiploid DNA peak was not. To verify whether the appearance of a hypodiploid DNA peak corresponded to apoptosis, we used in situ end labelling (ISEL) and transmission electron microscopy (TEM) in HEC-1A cells. We found that a 48-h treatment with genistein induced ISEL positivity only in a minority of cells, while at 72 h the majority of cells were labelled. At this time TEM showed the typical ultrastructural features of apoptosis, including apoptotic bodies.
Because genistein inhibited tyrosine kinase (TK) and topoisomerase (Topo) II activity in HEC-1A cells and its effects were mimicked by structurally unrelated TK and Topo II inhibitors, we speculate that interactions with TK and Topo II are relevant for the antiproliferative effect of genistein. Conversely, the antiproliferative effect of genistein seems to be independent of its oestrogenic activity. Our data indicate that genistein inhibits the growth of uterine adenocarcinoma cell lines by inducing cell cycle arrest and apoptosis.
Endocrine-Related Cancer (1997) 4 203-218
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) was beyond the understanding and expectations of their proponents and opened the avenue of oestrogen deprivation as a means to block tumour growth. The selective efficacy of ovariectomy and adrenalectomy for respectively pre- and postmenopausal
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divided into two subtypes: oestrogen-dependent type I and the less common, but clinically more aggressive, oestrogen-independent type II ( Emons et al . 2000 ). Approximately 95% of endometrial tumours are adenocarcinomas arising due to malignant
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influence how we proceed in the future. Session 1 focused around oestrogen receptor-α (ERα) as an old target that has recently spawned the exciting third generation of aromatase inhibitors and where new knowledge of the molecular actions of the ER is
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apoptosis have been identified ( Dou et al. 2014 ). Many reports have suggested a relevant role of IFNγ/STAT1/IRF-1 axis in the endocrine resistance of oestrogen receptor (ER)-positive breast cancer cells ( Clarke et al. 2009 , Ning et al. 2010
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first and extremely successful targeted therapies in oncology could considered to be the development of anti-hormone therapies for breast and prostate cancer which blocked the action of the oestrogen receptor (ER) and androgen receptor respectively, with
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Dame Roma Mitchell Cancer Research Laboratories Discipline of Medicine, The University of Adelaide and Hanson Institute, DX 650801, Adelaide, South Australia 5005, Australia
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Dame Roma Mitchell Cancer Research Laboratories Discipline of Medicine, The University of Adelaide and Hanson Institute, DX 650801, Adelaide, South Australia 5005, Australia
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Dame Roma Mitchell Cancer Research Laboratories Discipline of Medicine, The University of Adelaide and Hanson Institute, DX 650801, Adelaide, South Australia 5005, Australia
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masculinising side effects in some women and the concurrent development of targeted anti-oestrogenic therapies. With recent insights into the molecular heterogeneity of breast cancers, intracrine steroid metabolism and mechanisms of anti-oestrogen therapy
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the cancer cells from an epithelial to a more invasive mesenchymal phenotype, which may promote the spread of these cells to the bone ( El-Haibi et al . 2012 ). In a cohort of patients with oestrogen receptor negative (ER−) breast cancers, primary
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Introduction Steroid-dependent diseases Breast cancer, a major cause of death in both European and American women, occurs most frequently in post-menopausal women. After menopause, a low level of oestrogen is produced, mainly from the local
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extraordinary extent of tumour regression in perhaps 1% of postmenopausal cases (with oestrogen) has always be regarded as of major theoretical importance and it is a matter for some disappointment that so much of the underlying mechanism continues to elude us