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二甲氧基雌二醇;二甲氧雌二醇

CAS No. : 362-07-2

MCE 国际站：2-Methoxyestradiol

产品活性：2-Methoxyestradiol (2-ME2)，具有口服活性的 17β-雌二醇 (E2) 的内源性代谢产物，是凋亡 (apoptosis) 诱导剂和血管生成 (angiogenesis) 抑制剂，具有有效的抗肿瘤活性。2-Methoxyestradiol 也可破坏微管 (microtubules) 的稳定。2-Methoxyestradiol 是一种有效的超氧化物歧化酶 (SOD) 抑制剂和活性氧生成剂，可诱导转化细胞系 HEK293、癌细胞系 U87 和 HeLa 的自噬 (autophagy)。

研究领域：Cytoskeleton  |  Cell Cycle/DNA Damage  |  Immunology/Inflammation  |  NF-κB  |  Apoptosis  |  Autophagy  |  Metabolic Enzyme/Protease

作用靶点：Microtubule/Tubulin  |  Reactive Oxygen Species  |  Apoptosis  |  Autophagy  |  Endogenous Metabolite

结构分类：酚类

In Vitro: 2-Methoxyestradiol (2-ME) (5-100 μM) inhibits assembly of purified tubulin in a concentration-dependent manner, with maximal inhibition (60%) at 200 μM 2-Methoxyestradiol (2ME2). In living interphase MCF7 cells at the IC₅₀ for mitotic arrest (1.2 μM), 2-Methoxyestradiol significantly suppresses the mean microtubule growth rate, duration and length, and the overall dynamicity, consistent with its effects in vitro, and without any observable depolymerization of microtubules. 2-Methoxyestradiol induces G₂-M arrest and apoptosis in many actively dividing cell types while sparing quiescent cells. 2-Methoxyestradiol binds to tubulin at or near the colchicine site, it inhibits microtubule assembly, and high concentrations have been shown to depolymerize microtubules in cells.
2-Methoxyestradiol (2-ME) decreases the HIF-1α and HIF-2α nuclear staining in cells cultured under hypoxia. 2-Methoxyestradiol is an anti-angiogenic, anti-proliferative and pro-apoptotic agent that suppresses HIF-1α protein levels and its transcriptional activity. A significant decrease in the growth rate is found in the 10 µM 2-Methoxyestradiol-treated A549 cells in comparison with the DMSO-treated cells (66.2±7.2 and 101.2±2.3%, respectively; p=0.04) at 96 h. A significant increase in apoptosis is observed in cells treated with 10 µM 2-Methoxyestradiol in a normoxic condition in comparison with cells under lower O₂ concentration (5.8±0.2%; p=0.003).

In Vivo: To investigate the effect of 2-Methoxyestradiol (2-ME2) on uveitis development, C57BL/6 mice are randomly assigned into two groups and immunized with IRBP peptide. 2ME2 group starts 2-Methoxyestradiol (15 mg/kg) intraperitoneally from day 0 to day 13 while control group is given with vehicle. The disease score of 2-Methoxyestradiol (2ME2) group is 0.30±0.30, significantly lower than that of control group 2.09±0.28 (p<0.05), each group containing 5 mice.
Treatment with 2-Methoxyestradiol (60-600 mg/kg/d) results in a dose-dependent inhibition of tumor growth. The percentage of cells with strong pimonidazole-positive staining (+++) is significantly decreased in the 2-Methoxyestradiol-treated group (36.0% for 60 mg/kg/d and 0% for 200 and 600 mg/kg/d) compare with the vehicle-treated group (86.5%). This may be attributed to the dramatic inhibition of tumor growth in a dose-dependent manner following 2-Methoxyestradiol treatment.

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