2-Methoxyestradiol (2-MeOE2/2-Me) is an HIF-1α inhibitor. It can inhibit the accumulation of HIF-1α nuclei and the transcription activity of HIF[1-3] .2-ME can trigger p53-induced apoptosis through 2 mechanisms: activation of P38 and NF-κB as well as activation of JNK and AP-1 which leads to phosphorylation of Bcl-2. It prevents mitosis of tumor cell by inhibiting tubulin assembly, destabilizing microtubules, and interfering with spindle mitosis. As an apoptosis inducer and an angiogenesis inhibitor with potential antineoplastic activity[4].
2-Methoxyestradiol (10 µg/mL;1-4days) treatment significantly inhibited the proliferation ability of B16 melanoma cells[5]. 2-Methoxyestradiol (0.03-33mM) abolished L-lactate-induced migration and proliferation of osteosarcoma cells[6].
2-Methoxyestradiol (30 mg/kg;i.p/p.o; 7days/3weeks) treatment prior to and post irradiation inhibited Radiation-induced skin injury (RISI) on the skin of C57/BL6 mice. 2-ME also reduced radiation-induced inflammation, skin thickness, and vascular fibrosis[7].
References:
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[2]. Ricker JL, Chen Z, et,al. 2-methoxyestradiol inhibits hypoxia-inducible factor 1alpha, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squamous cell carcinoma. Clin Cancer Res. 2004 Dec 15;10(24):8665-73. doi: 10.1158/1078-0432.CCR-04-1393. PMID: 15623651.
[3]. Tevaarwerk, A.J.; Holen, K.D.; et,al. Phase I trial of 2-Methoxyestradiol NanoCrystal dispersion in advanced solid malignancies. Clin. Cancer Res. 2009, 15, 1460-1465.
[4]. Fotsis T, Zhang Y, et,al. The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature. 1994 Mar 17;368(6468):237-9. doi: 10.1038/368237a0. PMID: 7511798.
[5]. Hua W, Huang X, et,al. 2-methoxyestradiol inhibits melanoma cell growth by activating adaptive immunity. Immunopharmacol Immunotoxicol. 2022 Aug;44(4):541-547. doi: 10.1080/08923973.2022.2062380. Epub 2022 Apr 22. PMID: 35451929.
[6]. Gorska-Ponikowska M, Kuban-Jankowska A, et,al. 2-Methoxyestradiol Reverses the Pro-Carcinogenic Effect of L-Lactate in Osteosarcoma 143B Cells. Cancer Genomics Proteomics. 2017 Nov-Dec;14(6):483-493. doi: 10.21873/cgp.20058. PMID: 29109098; PMCID: PMC6070326.
[7]. Kim JH, Nam JK, et,al. 2-Methoxyestradiol Inhibits Radiation-Induced Skin Injuries. Int J Mol Sci. 2022 Apr 10;23(8):4171. doi: 10.3390/ijms23084171. PMID: 35456989; PMCID: PMC9032705.
2-Methoxyestradiol (2-MeOE2/2-Me)是一种HIF-1α抑制剂。它可以抑制HIF-1α核的聚集和HIF的转录活性[1-3]。2-Methoxyestradiol可通过激活P38和NF-κB以及激活JNK和AP-1导致Bcl-2磷酸化两种机制触发p53诱导的细胞凋亡。它通过抑制微管蛋白组装、破坏微管稳定和干扰纺锤体有丝分裂来阻止肿瘤细胞的有丝分裂。作为细胞凋亡诱导剂和血管生成抑制剂,具有潜在的抗肿瘤活性[4]。
2-Methoxyestradiol(10 µg/mL;1-4days)处理显著抑制B16黑色素瘤细胞的增殖能力[5]。2-Methoxyestradiol (0.03-33mM)可消除L-乳酸诱导的骨肉瘤细胞的迁移和增殖[6]。
2-Methoxyestradiol (30 mg/kg;i.p/p.o; 7days/3weeks)辐照前后对C57/BL6小鼠皮肤的辐射性皮肤损伤(RISI)有抑制作用。2-ME还能减少辐射引起的炎症、皮肤厚度和血管纤维化[7]。