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Glioblastoma multiforme (GBM) is the most fatal cancer among brain tumors, and the standard treatment of GBM patients is surgical tumor resection followed by radiotherapy and temozolomide (TMZ) chemotherapy. However, tumors always recur due to the developing drug resistance. It has been shown that neurosteroids, including dehydroepiandrosterone and 17β-estradiol, are synthesized in TMZ-resistant GBM tumors. Therefore, we sought to explore the possible role of 17β-estradiol in the development of drug resistance in GBM. Bioinformatics analysis revealed that aromatase/cytochrome P450 19A1 expression was gradually increased in the development from normal, astrocytoma to GBM. The level of 17β-estradiol was significantly increased in TMZ-resistant cells characterized by ultra performance liquid chromatography-tandem mass spectrometry. Furthermore, 17β-estradiol attenuated TMZ-induced cell death and reduced reactive oxygen species production by mitochondria. In addition, 17β-estradiol attenuated oxidative stress by increasing the expression of superoxide dismutase 1/2, catalase, and nuclear factor erythroid 2-related factor (NRF) 2. We found that NRF2 expression was essential for the induction of drug resistance by 17β-estradiol through the reduction of oxidative stress in GBM.

Titel:	17β-estradiol induces temozolomide resistance through NRF2-mediated redox homeostasis in glioblastoma.
Autor/in / Beteiligte Person:	Lin, HY ; Liao, KH ; Ko, CY ; Chen, GY ; Hsu, SP ; Hung, CY ; Hsu, TI
Zeitschrift:	Free radical biology & medicine, Jg. 172 (2021-08-20), S. 430-440
Veröffentlichung:	Tarrytown, NY : Elsevier Science ; <i>Original Publication</i>: New York : Pergamon, c1987-, 2021
Medientyp:	academicJournal
ISSN:	1873-4596 (electronic)
DOI:	10.1016/j.freeradbiomed.2021.06.028
Schlagwort:	Apoptosis Cell Line, Tumor Drug Resistance, Neoplasm genetics Estradiol pharmacology Homeostasis Humans NF-E2-Related Factor 2 genetics Neoplasm Recurrence, Local Oxidation-Reduction Temozolomide pharmacology Brain Neoplasms genetics Glioblastoma drug therapy Glioblastoma genetics
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Free Radic Biol Med] 2021 Aug 20; Vol. 172, pp. 430-440. <i>Date of Electronic Publication: </i>2021 Jun 26. MeSH Terms: Brain Neoplasms* / genetics ; Glioblastoma* / drug therapy ; Glioblastoma* / genetics ; Apoptosis ; Cell Line, Tumor ; Drug Resistance, Neoplasm / genetics ; Estradiol / pharmacology ; Homeostasis ; Humans ; NF-E2-Related Factor 2 / genetics ; Neoplasm Recurrence, Local ; Oxidation-Reduction ; Temozolomide / pharmacology Contributed Indexing: Keywords: 17β-estradiol; Aromatase; Drug resistance; Glioblastoma; NRF2; Neurosteroid; Temozolomide Substance Nomenclature: 0 (NF-E2-Related Factor 2) ; 4TI98Z838E (Estradiol) ; YF1K15M17Y (Temozolomide) Entry Date(s): Date Created: 20210629 Date Completed: 20210826 Latest Revision: 20210826 Update Code: 20231215

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17β-estradiol induces temozolomide resistance through NRF2-mediated redox homeostasis in glioblastoma.