2-Methoxyestradiol (Synonyms: 二甲氧基雌二醇; 2-ME2; NSC-659853)

2-Methoxyestradiol (2-ME2)，具有口服活性的 17β-雌二醇 (E2) 的內(nèi)源性代謝產(chǎn)物，是凋亡 (apoptosis) 誘導劑和血管生成 (angiogenesis) 抑制劑，具有有效的抗腫瘤活性。2-Methoxyestradiol 也可破壞微管 (microtubules) 的穩(wěn)定。2-Methoxyestradiol 是一種有效的超氧化物歧化酶 (SOD) 抑制劑和活性氧生成劑，可誘導轉(zhuǎn)化細胞系 HEK293、癌細胞系 U87 和 HeLa 的自噬 (autophagy)。

生物活性

2-Methoxyestradiol (2-ME2), an orally active endogenous metabolite of 17β-estradiol (E2), is an apoptosis inducer and an angiogenesis inhibitor with potent antineoplastic activity. 2-Methoxyestradiol also destablize microtubules. 2-Methoxyestradio, also a potent superoxide dismutase (SOD) inhibitor and a ROS-generating agent, induces autophagy in the transformed cell line HEK293 and the cancer cell lines U87 and HeLa

IC₅₀ & Target

Human Endogenous Metabolite

體外研究(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^[1].
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)^[2].

體內(nèi)研究(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^[3].
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^[4].

分子量：302.41

Formula：C₁₉H₂₆O₃

CAS 號：362-07-2

中文名稱：二甲氧基雌二醇；二甲氧雌二醇

運輸條件：Room temperature in continental US; may vary elsewhere.

儲存方式

溶解性數(shù)據(jù)

參考文獻

[1]. Kamath K, et al. 2-Methoxyestradiol suppresses microtubule dynamics and arrests mitosis without depolymerizing microtubules. Mol Cancer Ther. 2006 Sep;5(9):2225-33.

[2]. Aquino-Gálvez A, et al. Effects of 2-methoxyestradiol on apoptosis and HIF-1α and HIF-2α expression in lung cancer cells under normoxia and hypoxia. Oncol Rep. 2016 Jan;35(1):577-83.

[3]. Xu L, et al. 2-Methoxyestradiol Alleviates Experimental Autoimmune Uveitis by Inhibiting Lymphocytes Proliferation and T Cell Differentiation. Biomed Res Int. 2016;2016:7948345.

[4]. Kang SH, et al. Antitumor effect of 2-methoxyestradiol in a rat orthotopic brain tumor model. Cancer Res. 2006, 66(24),11991-11997.

[5]. LaVallee TM, et al. 2-Methoxyestradiol inhibits proliferation and induces apoptosis independently of estrogen receptorsalpha and beta. Cancer Res. 2002 Jul 1;62(13):3691-7.

[6]. Chen Y, et al. Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells. Cell Death Differ. 2008;15(1):171-182.