2-methoxyestradiol induces interferon gene expression and apoptosis in osteosarcoma cells

Maran, Avudaiappan; Zhang, M; Kennedy, Angela M.; Sibonga, Jean D.; Rickard, David J.; Spelsberg, Thomas C.; Turner, Russell T.

doi:10.1016/s8756-3282(01)00681-0

Cited by 40 publications

(65 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 Moreover, despite its being a natural derivative of estradiol (E2), 2ME2 binds poorly to the ERs; therefore, the antiproliferative effects of 2ME2 are not mediated by ERs. 12,13 These findings, coupled with our studies, suggest that 2ME2-mediated effects on MM cells are independent of ER.Previous studies using xenografts and metastatic disease models in mice have suggested that 2ME2 targets not only the tumor cell but also the tumor vasculature. 2,14 Recent reports of increased bone marrow (BM) angiogenesis in multiple myeloma (MM), [15][16][17] coupled with the known antiangiogenic properties of 2ME2, 2,14 provide a potential rationale for evaluating 2ME2 as a novel therapeutic in MM.…”

supporting

confidence: 76%

2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells

Chauhan

Catley

Hideshima

et al. 2002

Blood

110

View full text Add to dashboard Cite

2-Methoxyestradiol (2ME2) an estrogen derivative, induces growth arrest and apoptosis in leukemic cells and is also antiangiogenic. In this study, we demonstrate that 2ME2 inhibits growth and induces apoptosis in multiple myeloma (MM) cell lines and patient cells. Significantly, 2ME2 also inhibits growth and induces apoptosis in MM cells resistant to conventional therapies including melphalan (LR-5), doxorubicin (Dox-40 and Dox-6), and dexamethasone (MM.1R). In contrast to its effects on MM cells, 2ME2 does not reduce the survival of normal peripheral blood lymphocytes. Moreover, 2ME2 enhances Dex-induced apoptosis, and its effect is not blocked by interleukin-6 (IL-6). We next examined the effect of 2ME2 on MM cells in the bone marrow (BM) milieu. 2ME2 decreases survival of BM stromal cells (BMSCs), as well as secretion of vascular endothelial growth factor (VEGF), and IL-6 triggered by the adhesion of MM cells to BMSCs. We show that apoptosis induced by 2ME2 is mediated by the release of mitochondrial cytochrome-c (cyto-c) and Smac, followed by the activation of caspases-8, -9, and -3. Finally, 2ME2 inhibits MM cell growth, prolongs survival, and decreases angiogenesis in a murine model. These studies, therefore, demonstrate that 2ME2 mediates anti-MM activity directly on MM cells and in the BM microenvironment. They provide a framework for the use of 2ME2, either alone or in combination with Dex, to overcome drug resistance and to improve outcome in MM.

show abstract

supporting

confidence: 76%

2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells

Chauhan

Catley

Hideshima

et al. 2002

Blood

110

View full text Add to dashboard Cite

show abstract

“…2-Methoxyestradiol (2ME2) is a natural estrogen metabolite of E2 that has no estrogenic effects itself but has both antiangiogenic and antitumorigenic effects [Fotsis et al, 1994;Lin et al, 2001;Schumacher and Neuhaus, 2001;Carothers et al, 2002], including effects on osteosarcoma [Maran et al, 2002] and Ewing sarcoma [Djavaheri-Mergny et al, 2003]. Both microvasculature and large vessel endothelial cell proliferation are also blocked by 2ME2 [Fotsis et al, 1994].…”

Section: The Hormonal Milieu During Pregnancymentioning

confidence: 99%

The role of steroid hormones in the NF1 phenotype: Focus on pregnancy

Roth

Petty

Barald

2008

American J of Med Genetics Pt A

View full text Add to dashboard Cite

The Neurofibromatosis Type 1 (NF1) gene functions as a tumor suppressor gene. Loss of its protein, neurofibromin, in the autosomal dominant disorder NF1 is associated with peripheral nervous system tumors, particularly neurofibromas, benign lesions in which the major cell type is the Schwann Cell (SC). Benign and malignant human tumors found in NF1 patients are heterogeneous with respect to their cellular composition. The number and size of neurofibromas in NF1 patients has been shown to increase during pregnancy, with, in some cases, post-partum regression, which suggests hormonal involvement in this increase. However, in this review, we consider evidence from the literature that both direct hormonal influence on tumor growth and on angiogenesis may contribute to these effects.

show abstract

“…Since the mechanism of action of 2-ME is multifaceted and appears to vary according to cell type 2,5,11,24 the aim of this study was to investigate the mechanism of action of 2-ME in an oesophageal carcinoma cell line by determining its influence on cell numbers, morphology, cell cycle progression, and apoptosis induction. …”

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

View full text Add to dashboard Cite

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.

show abstract

2-methoxyestradiol induces interferon gene expression and apoptosis in osteosarcoma cells

Cited by 40 publications

References 23 publications

2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells

2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells

The role of steroid hormones in the NF1 phenotype: Focus on pregnancy

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

Contact Info

Product

Resources

About