ArticleCancer chemotherapy and pharmacology2022
Potentiation of temozolomide activity against glioblastoma cells by aromatase inhibitor letrozole.
Article in Cancer chemotherapy and pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Pro-Synergistic Interaction of Farnesene and Daunorubicin Enhances Apoptotic Vulnerability in U87MG Glioblastoma Cells.Cell biochemistry and biophysics · 2026Article
- Preclinical Evaluation of the Efficacy of the Cyclin-Dependent Kinase Inhibitor Ribociclib in Combination with Letrozole against Patient-Derived Glioblastoma Cells.Molecular cancer therapeutics · 2026Article
- Review
- Rapid Biofabrication of an Advanced Microphysiological System Mimicking Phenotypical Heterogeneity and Drug Resistance in Glioblastoma.Advanced healthcare materials · 2024Article
- A Phase 0/I Pharmacokinetic and Pharmacodynamics and Safety and Tolerability Study of Letrozole in Combination with Standard Therapy in Recurrent High-Grade Gliomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- A Review of Approaches to Potentiate the Activity of Temozolomide against Glioblastoma to Overcome Resistance.International journal of molecular sciences · 2024Review
- CDS-DB, an omnibus for patient-derived gene expression signatures induced by cancer treatment.Nucleic acids research · 2024Article
- Novel Natural Inhibitors for Glioblastoma by Targeting Epidermal Growth Factor Receptor and Phosphoinositide 3-kinase.Current medicinal chemistry · 2024Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
purposeThe DNA alkylating agent temozolomide (TMZ), is the first-line therapeutic for the treatment of glioblastoma (GBM). However, its use is confounded by the occurrence of drug resistance and debilitating adverse effects. Previously, we observed that letrozole (LTZ), an aromatase inhibitor, has potent activity against GBM in pre-clinical models. Here, we evaluated the effect of LTZ on TMZ activity against patient-derived GBM cells.
methodsEmploying patient-derived G76 (TMZ-sensitive), BT142 (TMZ-intermediately sensitive) and G43 and G75 (TMZ-resistant) GBM lines we assessed the influence of LTZ and TMZ on cell viability and neurosphere growth. Combination Index (CI) analysis was performed to gain quantitative insights of this interaction. We then assessed DNA damaging effects by conducting flow-cytometric analysis of ˠH2A.X formation and induction of apoptotic signaling pathways (caspase3/7 activity). The effects of adding estradiol on LTZ-induced cytotoxicity and DNA damage were also evaluated.
resultsCo-treatment with LTZ at a non-cytotoxic concentration (40 nM) reduced TMZ IC
conclusionsLTZ increases DNA damage and synergistically enhances TMZ activity in TMZ sensitive and TMZ-resistant GBM lines. These effects are abrogated by the addition of exogenous estradiol underscoring that the observed effects of LTZ may be mediated by estrogen deprivation. Our study provides a strong rationale for investigating the clinical potential of combining LTZ and TMZ for GBM therapy.
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