The endogenous estrogen metabolite 2-methoxyestradiol induces apoptotic neuronal cell death in vitro

Nakagawa-Yagi, Yuzo; Ogane, Nobuo; Inoki, Yutaka; Kitoh, Naomi

doi:10.1016/0024-3205(96)00116-6

Cited by 34 publications

(16 citation statements)

References 8 publications

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“…Furthermore, the single metastatic lesions were signi®cantly smaller in the treatment group (Schumacher 1999). Neuroblastoma has been observed to be sensitive to 2-ME in a dose-dependent manner (Wassberg 1999;Nakagawa-Yagi 1996). Angiosarcoma as an endothelial tumor also appeared to be a good target for 2-ME, which could be inhibited by 50±84% (Arbiser 1999;Reiser 1998).…”

Section: Introductionmentioning

confidence: 91%

The physiological estrogen metabolite 2-methoxyestradiol reduces tumor growth and induces apoptosis in human solid tumors

Schumacher

Neuhaus

2001

Journal of Cancer Research and Clinical Oncology

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2-Methoxyestradiol (2-ME) is a physiological metabolite of estrogen, which is excreted with the urine. In contrast to most estrogens, tumor growth-inhibiting effects were observed. Further studies have revealed that it may be an effective anticancer compound for many tumor types. Several different mechanisms have been attributed to 2-ME. Besides a strong antiangiogenic effect on endothelial cells and tumors, there is a tubulin-inhibiting mechanism, causing cells to arrest in the G2/ M phase of the cell cycle. In other tumors, p53-dependent and p53-independent mechanisms with induction of apoptosis have been shown. The number of different tumors examined for a growth-inhibiting effect is increasing, and new mechanisms are continuously described. In vivo studies in mice, rats, and dogs show no or very little toxicity, even at high doses. Here, we discuss the antitumor activity and their mechanisms. 2-ME appears to be a new anti-tumor compound with strong potential for clinical application.

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Section: Introductionmentioning

confidence: 91%

The physiological estrogen metabolite 2-methoxyestradiol reduces tumor growth and induces apoptosis in human solid tumors

Schumacher

Neuhaus

2001

Journal of Cancer Research and Clinical Oncology

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“…[5][6][7] Accordingly, this endogenous estradiol metabolite has manifested as a potential anticancer agent. 5 Current evidence has suggested that 2-ME is the causative agent leading to an increase in Cdc2 kinase activity, the activation of c-Jun NH 2 -terminal kinase signaling, generation of reactive oxygen species and an altered ratio of Bax/ Bcl-2 in favor of Bax, ultimately culminating into apoptosis.…”

Section: Introductionmentioning

confidence: 99%

In vitro effects of 2‐methoxyestradiol on cell numbers, morphology, cell cycle progression, and apoptosis induction in oesophageal carcinoma cells

Thaver

Lottering

Papendorp

et al. 2009

Cell Biochemistry & Function

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The influence of 2-methoxyestradiol (2-ME) was investigated on cell numbers, morphology, cell cycle progression, and apoptosis induction in an oesophageal carcinoma cell line (WHCO3). Dose-dependent studies (1 x 10(-9)M-1 x 10(-6)M) revealed that 2-ME significantly reduced cell numbers to 60% in WHCO3 after 72 h of exposure at a concentration of 1 x 10(-6)M compared to vehicle-treated cells. Morphological studies entailing light-, fluorescent-, as well as transmission electron microscopy (TEM) confirmed 2-ME's antimitotic effects. These results indicated hallmarks of apoptosis including cell shrinkage, hypercondensation of chromatin, cell membrane blebbing, and apoptotic bodies in treated cells. Flow cytometric analyses demonstrated an increase in the G(2)/M-phase after 2-ME exposure; thus preventing cells from proceeding through the cell cycle. beta-tubulin immunofluorescence revealed that 2-ME caused spindle disruption. In addition, increased expression of death receptor 5 protein was observed further supporting the proposed mechanism of apoptosis induction via the extrinsic pathway in 2-ME-exposed oesophageal carcinoma cells.

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“…Two-methoxyestradiol has anti-angiogenic properties that were demonstrated both in vivo as well as in vitro [15, 16]. Two-methoxyestradiol has also been shown to exhibit pro-apoptotic and anti-proliferative properties in a variety of cells in vitro [17].…”

Section: Introductionmentioning

confidence: 99%

Whole flaxseed diet alters estrogen metabolism to promote 2-methoxtestradiol-induced apoptosis in hen ovarian cancer

Dikshit

Hales

2017

The Journal of Nutritional Biochemistry

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The study reported here demonstrates that a flaxseed supplemented diet causes ovarian tumors in the laying hen to undergo apoptosis, resulting in a reduction of tumor burden, reducing the frequency and severity of ovarian cancer. We have previously shown in normal ovaries that flaxseed and its components downregulate ERalpha and alter the expression of enzymes that metabolize estrogen. In this study, we analyzed the effects of the two main components of whole flaxseed, ligan and omega 3 fatty acids, on estrogen metabolism and the estrogen receptor in ovarian tumors. ER alpha expression was upregulated in the ovarian tumors and was not affected by diet. Liver CYP1A1 expression was significantly increased by the whole flaxseed diet with a corresponding increase in 2-methoxyestradiol plasma levels. We also observed increased p38 and ERK 1/2 MAPK activation in the ovary as well as an increase in apoptosis in the tumor epithelium. SMAD 7, a factor involved in the 2-methoxyestradiol-mediated apoptosis pathway was also upregulated in tumors from the whole flaxseed diet group. 2-methoxyestradiol-induced anti-tumor effects were further validated by in human ovarian cancer cells. This study details the effect of flaxseed diet on estrogen metabolism and demonstrates the anti-ovarian cancer effects of 2-methoxyestradiol.

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The endogenous estrogen metabolite 2-methoxyestradiol induces apoptotic neuronal cell death in vitro

Cited by 34 publications

References 8 publications

The physiological estrogen metabolite 2-methoxyestradiol reduces tumor growth and induces apoptosis in human solid tumors

The physiological estrogen metabolite 2-methoxyestradiol reduces tumor growth and induces apoptosis in human solid tumors

In vitro effects of 2‐methoxyestradiol on cell numbers, morphology, cell cycle progression, and apoptosis induction in oesophageal carcinoma cells

Whole flaxseed diet alters estrogen metabolism to promote 2-methoxtestradiol-induced apoptosis in hen ovarian cancer

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