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2-methoxyestradiol

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https://www.readbyqxmd.com/read/28624453/folic-acid-attenuates-cobalt-chloride-induced-pge2-production-in-huvecs-via-the-no-hif-1alpha-cox-2-pathway
#1
Yuming Liang, Xiaozhou Zhen, Kaiwen Wang, Jing Ma
Prostaglandin E2 (PGE2), an important lipid inflammatory mediator involved in the progression of vascular diseases, can be induced by hypoxia in many cell types. While folic acid has been shown to protect against inflammation in THP-1 cells duringpo hypoxia and hypoxia-induced endothelial cell injury, whether it might do so by attenuating PGE2 production remains unclear. To investigate this we constructed a hypoxia-induced injury model by treating human umbilical vein endothelial cells (HUVECs) with cobalt chloride (CoCl2), which mimics the effects of hypoxia...
June 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28612593/2-methoxyestradiol-promotes-radiosensitivity-of-esophageal-squamous-cell-carcinoma-by-suppressing-hypoxia-inducible-factor-1%C3%AE-expression
#2
Yanrong Lu, Jia Song, Zhabihula Baerxiaguli, Zengyan Li, Min Wu, Jinrong Zhang
Background: Acquired radioresistance remains a primary obstacle to improving survival of patients with esophageal cancer(EC). Factors related to hypoxia play crucial roles in such radioresistance, such as hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF) and angiogenic factor with G-patch and FHA domains 1 (AGGF1). However, evidence clarifying the role of AGGF1 in EC is limited. We here aimed to investigate the effects of 2-methoxyestradiol(2ME2) on the radiosensitivity of EC...
May 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28565876/effects-of-17%C3%AE-estradiol-and-2-methoxyestradiol-on-the-oxidative-stress-hypoxia-inducible-factor-1-pathway-in-hypoxic-pulmonary-hypertensive-rats
#3
Li Wang, Quan Zheng, Yadong Yuan, Yanpeng Li, Xiaowei Gong
The present study aimed to investigate the effects of 17β-estradiol (E2) and 2-methoxyestradiol (2ME) on the oxidative stress-hypoxia inducible factor-1 (OS-HIF-1) pathway in hypoxic pulmonary hypertensive rats. Female Sprague-Dawley rats were divided randomly into 4 groups, as follows: i) Control (Group A); ii) ovariectomy (OVX) + hypoxia (Group B); iii) OVX + hypoxia + E2 injection (Group C); and iv) 2ME injection (Group D). The rats were maintained under hypoxic conditions for 8 weeks, and mean pulmonary artery pressure (mPAP) and pulmonary arteriole morphology were measured...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28555342/microchip-electrophoresis-with-laser-induced-fluorescence-detection-for-the-determination-of-the-ratio-of-nitric-oxide-to-superoxide-production-in-macrophages-during-inflammation
#4
Giuseppe Caruso, Claudia G Fresta, Joseph M Siegel, Manjula B Wijesinghe, Susan M Lunte
It is well known that excessive production of reactive oxygen and nitrogen species is linked to the development of oxidative stress-driven disorders. In particular, nitric oxide (NO) and superoxide (O2(•-)) play critical roles in many physiological and pathological processes. This article reports the use of 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate and MitoSOX Red in conjunction with microchip electrophoresis and laser-induced fluorescence detection for the simultaneous detection of NO and O2(•-) in RAW 264...
May 29, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28536432/nuclear-translocation-of-hif-1%C3%AE-induced-by-influenza-a-h1n1-infection-is-critical-to-the-production-of-proinflammatory-cytokines
#5
Xinkun Guo, Zhaoqin Zhu, Wanju Zhang, Xiaoxiao Meng, Yong Zhu, Peng Han, Xiaohui Zhou, Yunwen Hu, Ruilan Wang
Infection with the influenza A (H1N1) virus is a major challenge for public health because it can cause severe morbidity and even mortality in humans. The over-secretion of inflammatory cytokines (cytokine storm) is considered to be a key contributor to the severe pneumonia caused by H1N1 infection. It has been reported that hypoxia-inducible factor 1-alpha (HIF-1α) is associated with the production of proinflammatory molecules, but whether HIF-1α participates in the acute inflammatory responses against H1N1 infection is still unclear...
May 24, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28536143/aurora-kinase-a-promotes-ar-degradation-via-the-e3-ligase-chip
#6
Sukumar Sarkar, David L Brautigan, James M Larner
Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer (CRPC). Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation...
May 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28511459/a-comparison-of-2-methoxyestradiol-value-in-women-with-severe-preeclampsia-versus-normotensive-pregnancy
#7
John Wantania, Ahsanuddin Attamimi, Rukmono Siswishanto
INTRODUCTION: Preeclampsia is a pregnancy complication characterized by high blood pressure and proteinuria. Endothelial dysfunction is a major theory suggested as its aetiology. It is caused by anti-angiogenic condition characterized by low Vascular Endothelial Growth Factor (VEGF). An estradiol metabolite, called 2-Methoxy Estradiol (2-ME), is produced with the help of Catechol-O-Methyltransferase (COMT). This substance has an important role in VEGF expression. A 2-ME is suppressed in women with preeclampsia...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28461606/catechol-o-methyltransferase-deficiency-leads-to-hypersensitivity-of-the-pressor-response-against-angiotensin-ii
#8
Norikazu Ueki, Keizo Kanasaki, Megumi Kanasaki, Satoru Takeda, Daisuke Koya
Catechol-O-methyltransferase (COMT) metabolizes 2-hydroxyestradiol into 2-methoxyestradiol (2-ME); COMT deficiency has shown to be associated with hypertension in men and preeclampsia, the disease associated with hypersensitivity of pressor response against angiotensin II (Ang II). Here, we found that COMT deficiency could explain the hypersensitivity of pressor response against Ang II in mice because of the lack of 2-ME-dependent suppression of angiotensin II receptor type 1 (AT1R). Male C57BL/6 mice were subjected to COMT inhibitor (COMTi: 25 mg/kg per day) or oil (control) for 4 weeks, with or without low-dose Ang II infusion (ANGII: 70 ng/kg per minute) for the last 3 weeks...
June 2017: Hypertension
https://www.readbyqxmd.com/read/28416586/2-methoxyestradiol-a-17%C3%AE-estradiol-metabolite-with-gender-independent-therapeutic-potential
#9
EDITORIAL
Raghvendra K Dubey
No abstract text is available yet for this article.
June 2017: Hypertension
https://www.readbyqxmd.com/read/28416584/2-methoxyestradiol-reduces-angiotensin-ii-induced-hypertension-and-renal-dysfunction-in-ovariectomized-female-and-intact-male-mice
#10
Ajeeth K Pingili, Karen N Davidge, Shyamala Thirunavukkarasu, Nayaab S Khan, Akemi Katsurada, Dewan S A Majid, Frank J Gonzalez, L Gabriel Navar, Kafait U Malik
Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol. This study was conducted to determine whether 2-methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and end-organ damage in intact Cyp1b1(-/-), ovariectomized female, and Cyp1b1(+/+) male mice. Ang II or vehicle was infused for 2 weeks and administered concurrently with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II infusion for urine collection for 24 hours...
June 2017: Hypertension
https://www.readbyqxmd.com/read/28410397/a-bis-sulphamoylated-estradiol-derivative-induces-ros-dependent-cell-cycle-abnormalities-and-subsequent-apoptosis
#11
Michelle Helen Visagie, Iman van den Bout, Anna Margaretha Joubert
Clinical trials have revealed that the potential anticancer agent, 2-methoxyestradiol (2ME2) has limitations due to its low bioavailability. Subsequently, 2ME2 derivatives including (8R,13S,14S,17S)-2-ethyl-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrane-3,17-diyl bis(sulphamate) (EMBS) have shown improved efficacies in inducing apoptosis. However, no conclusive data exist to explain the mode of action exerted by these drugs. This study investigated the mode of action used by EMBS as a representative of the sulphamoylated 2ME2 derivatives...
2017: PloS One
https://www.readbyqxmd.com/read/28396280/high-oral-bioavailability-of-2-methoxyestradiol-in-peg-plga-micelles-microspheres-for-cancer-therapy
#12
XinHong Guo, CaiPing Chen, Xin Liu, PanPan Hou, XiaoNan Guo, Fang Ding, ZhiHao Wang, YuRong Hu, Zhi Li, ZhenZhong Zhang
The development of effective oral preparations of 2-methoxyestradiol (2-ME) has been a worldwide problem. In this study, breakthrough progress has been made in oral delivery of 2-ME by encapsulating 2-ME micelles in pH-responsive microspheres. 2-ME micelles with small particle size (58 nm) and high drug loading (7.94±0.23%) were successfully prepared and showed slower release characteristics and 12.8 times higher cytotoxicity on 4T1 cells than free 2-ME. The pH-sensitive microspheres could slowly release 82% of 2-ME micelles for 10 h in PBS (7...
April 7, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28376733/efficacy-of-intravitreal-injection-of-2-methoxyestradiol-in-regression-of-neovascularization-of-a-retinopathy-of-prematurity-rat-model
#13
Azza Mohamed Ahmed Said, Rania Gamal Eldin Zaki, Rania A Salah Eldin, Maha Nasr, Samar Saad Azab, Yaser Abdelmageuid Elzankalony
BACKGROUND: Retinopathy of prematurity (ROP) is one of the targets for early detection and treatment to prevent childhood blindness in world health organization programs. The purpose of study was to evaluate the efficacy of intravitreal injection of 2-Methoxyestradiol (2-ME) nanoemulsion in regressing neovascularization of a ROP rat model. METHODS: A prospective comparative case - control animal study conducted on 56 eyes of 28 healthy new born Sprague Dawley male albino rat...
April 4, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/28339028/2-methoxyestradiol-enhances-radiosensitivity-in-radioresistant-melanoma-mda-mb-435r-cells-by-regulating-glycolysis-via-hif-1%C3%AE-pdk1-axis
#14
Hong Zhao, Huangang Jiang, Zheng Li, Yafei Zhuang, Yinyin Liu, Shuliang Zhou, Youde Xiao, Conghua Xie, Fuxiang Zhou, Yunfeng Zhou
HIF-1α overexpression is associated with radio-resistance of various cancers. A radioresistant human melanoma cell model MDA-MB-435R (435R) was established by us previously. Compared with the parental cells MDA-MB‑435 (435S), an elevated level of HIF-1α expression in 435R cells was demonstrated in our recent experiments. Therefore, in the current study, we sought to determine whether selective HIF-1α inhibitors could radiosensitize the 435R cells to X-ray, and to identify the potential mechanisms. Our data demonstrated that inhibition of HIF-1α with 2-methoxyestradiol (2-MeOE2) significantly enhanced radiosensitivity of 435R cells...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28262924/2-methoxyestradiol-impacts-on-amino-acids-mediated-metabolic-reprogramming-in-osteosarcoma-cells-by-its-interaction-with-nmda-receptor
#15
Magdalena Gorska-Ponikowska, Ugo Perricone, Alicja Kuban-Jankowska, Giosuè Lo Bosco, Giampaolo Barone
Deregulation of serine and glycine metabolism, have been identified to function as metabolic regulators in supporting tumor cell growth. The role of serine and glycine in regulation of cancer cell proliferation is complicated, dependent on concentrations of amino acids and tissue-specific. D-serine and glycine are coagonists of N-methyl-D-aspartate (NMDA) receptor subunit GRIN1. Importantly, NMDA receptors are widely expressed in cancer cells and play an important role in regulation of cell death, proliferation, and metabolism of numerous malignancies...
March 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28259912/role-of-hypoxia%C3%A2-inducible-factor%C3%A2-1%C3%AE-in-autophagic-cell-death-in-microglial-cells-induced-by-hypoxia
#16
Xintao Wang, Jun Ma, Qiang Fu, Lei Zhu, Zhiling Zhang, Fan Zhang, Nan Lu, Aimin Chen
Microglial cells are phagocytic cells of the central nervous system (CNS) and have been proposed to be a primary component of the innate immune response and maintain efficient CNS homeostasis. Microglial cells are activated during various phases of tissue repair and participate in various pathological conditions in the CNS. Following spinal cord injury (SCI), anoxemia is a key problem that results in tissue destruction. Hypoxia‑inducible factor 1‑α (HIF‑1α) may protect hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28258163/g-1-inhibits-breast-cancer-cell-growth-via-targeting-colchicine-binding-site-of-tubulin-to-interfere-with-microtubule-assembly
#17
Xiangmin Lv, Chunbo He, Cong Huang, Guohua Hua, Zhengfeng Wang, Steven W Remmenga, Kerry J Rodabough, Adam R Karpf, Jixin Dong, John S Davis, Cheng Wang
G-protein-coupled estrogen receptor 1 (GPER1) has been reported to play a significant role in mediating the rapid estrogen actions in a wide range of normal and cancer cells. G-1 was initially developed as a selective agonist for GPER. However, the molecular mechanisms underlying the actions of G-1 are unknown, and recent studies report inconsistent effects of G-1 on the growth of breast cancer cells. By employing high-resolution laser scanning confocal microscopy and time-lapse imaging technology, as well as biochemical analyses, in the current study, we provide convincing in vitro and in vivo evidence that G-1 is able to suppress the growth of breast cancer cells independent of the expression status of GPERs and classic estrogen receptors...
June 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28242743/advances-in-hypoxia-mediated-mechanisms-in-hepatocellular-carcinoma
#18
Xin Xin Xiong, Xin Yao Qiu, Dian Xing Hu, Xiao Qian Chen
Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly malignant tumor worldwide. Hypoxia and related oxidative stress are heavily involved in the process of HCC development and therapies. However, direct and accurate measuring oxygen concentration and evaluating hypoxic effects in HCC prove difficult. Moreover, the hypoxia-mediated mechanisms in HCC remain elusive. Here, we summarize recent major evidence of hypoxia in HCC lesions by measuring pO2, the clinical importance of hypoxic markers in HCC, and recent advances in hypoxia-related mechanisms and therapies in HCC...
February 27, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28214650/2-methoxyestradiol-protects-against-igg-immune-complex-induced-acute-lung-injury-by-blocking-nf-%C3%AE%C2%BAb-and-ccaat-enhancer-binding-protein-%C3%AE-activities
#19
Chunguang Yan, Yanfei Shen, Qiqing Sun, Dong Yuan, Huifang Tang, Hongwei Gao
Increasing evidences indicate that 2-Methoxyestradiol (2ME2) plays an essential role in protecting against inflammatory responses. However, its effect on IgG immune complex (IC)-induced acute lung injury (ALI) remains enigmatic. In the study, by using i.p. administration of 2ME2, we evaluated its influence on IgG IC-induced pulmonary injury in mice. We found that during IgG IC-induced ALI, mice treated by 2ME2 displayed a substantial decrease in vascular permeability and neutrophil influx (represented by myeloperoxidase activity) when compared with their counterparts receiving vehicle treatment...
February 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28213273/2-methoxyestradiol-protects-against-ischemia-reperfusion-injury-in-alcoholic-fatty-liver-by-enhancing-sirtuin-1-mediated-autophagy
#20
Hong-Ik Cho, Min-Jong Seo, Sun-Mee Lee
Alcoholic fatty liver (AFL) is susceptible to ischemia/reperfusion (I/R) injury, responding with inflammation and extensive hepatocellular damage. Autophagy maintains cellular homeostasis and regulates inflammation and lipid metabolism. 2-Methoxyestradiol (2-ME2), an endogenous metabolite of estradiol, exhibits antioxidant and anti-inflammatory properties. This study examined the cytoprotective mechanisms of 2-ME2 on hepatic I/R in AFL, focusing on autophagy signaling. C57BL/6 mice were fed an ethanol diet (ED) to induce AFL, or a control diet (CD) for 6weeks, and then subjected to 60min of ischemia and 5h of reperfusion...
May 1, 2017: Biochemical Pharmacology
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