PMID: 19149482Jan 20, 2009Paper

2-methoxyestradiol as a potential cytostatic drug in gliomas?

Anti-cancer Agents in Medicinal Chemistry
E Kirches, M Warich-Kirches

Abstract

Gliomas of astrocytic origin show only a limited chemotherapy response. Chemoresistance is most pronounced in glioblastoma multiforme, the most common and most malignant glioma, with median survival times not much longer than one year. Failure of chemotherapy partly relies on protective mechanisms against the commonly used DNA alkylating agents, but also on the constitutive activation of the pro-survival PI3K-Akt pathway in glioma cells, which inhibits apoptosis. Therefore, new drugs with an alternative mechanism, independent of DNA alkylation, are required. The microtubule targeting drug 2-methoxyestradiol (2-ME) efficiently induces mitotic arrest, apoptosis, but also autophagic cell death in glioma cells in vitro. Moreover, it may be able to inhibit vascularization of the highly vascular gliobastomas, because the drug influences blood vessel sprouting via a HIF-1-dependent mechanism. Although high doses of i.p. injected 2-ME were recently shown to be effective in an orthothopic rat glioma model, clinical phase I/II trials revealed low oral bioavailability. One of the most exciting future perspectives will be the currently ongoing development of improved 2-ME analogs. Compounds, sulphamoylated at positions 3 and 17, combine su...Continue Reading

Citations

Apr 5, 2014·Journal of Neuro-oncology·Gabriella M AnicKathleen M Egan
Nov 15, 2011·Vascular Pharmacology·Boris A GorshkovNatalia V Bogatcheva
Oct 11, 2020·International Journal of Molecular Sciences·Maria PeleliAndreas Papapetropoulos
Sep 16, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Geoffrey C KabatThomas E Rohan
Mar 6, 2021·Critical Reviews in Oncology/hematology·Alja ZottelRadovan Komel
Aug 2, 2021·Cellular and Molecular Life Sciences : CMLS·Mariana MedeirosMaría Sol Brassesco

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