ArticleCancers2019
Arsenic Trioxide and (-)-Gossypol Synergistically Target Glioma Stem-Like Cells via Inhibition of Hedgehog and Notch Signaling.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Molecular insights into DNA damage response plasticity in glioma stem cells.Communications biology · 2026Review
- Review
- Review
- BRAT1 - a new therapeutic target for glioblastoma.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- Review
- Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy.Biomolecules · 2024Review
- Targeting Notch signaling pathways with natural bioactive compounds: a promising approach against cancer.Frontiers in pharmacology · 2024Review
- Combining organotypic tissue culture with light-sheet microscopy (OTCxLSFM) to study glioma invasion.EMBO reports · 2023Article
- Molecular Determinants of Calcitriol Signaling and Sensitivity in Glioma Stem-like Cells.Cancers · 2023Article
- Advances in mitophagy and mitochondrial apoptosis pathway-related drugs in glioblastoma treatment.Frontiers in pharmacology · 2023Review
- Arsenic Trioxide Triggers Apoptosis of Metastatic Oral Squamous Cells Carcinoma with Concomitant Downregulation of GLI1 in Hedgehog Signaling.Biomedicines · 2022Article
- Article
- Antitumor Effects of a New Retinoate of the Fungal Cytotoxin Illudin M in Brain Tumor Models.International journal of molecular sciences · 2022Article
- Current Advances of Nanomedicines Delivering Arsenic Trioxide for Enhanced Tumor Therapy.Pharmaceutics · 2022Review
- Mineral medicine: from traditional drugs to multifunctional delivery systems.Chinese medicine · 2022Review
- STAT3 Enhances Sensitivity of Glioblastoma to Drug-Induced Autophagy-Dependent Cell Death.Cancers · 2022Article
- Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide.Cancers · 2021Article
- Article
- Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Glioblastoma is one of the deadliest malignancies and is virtually incurable. Accumulating evidence indicates that a small population of cells with a stem-like phenotype is the major culprit of tumor recurrence. Enhanced DNA repair capacity and expression of stemness marker genes are the main characteristics of these cells. Elimination of this population might delay or prevent tumor recurrence following radiochemotherapy. The aim of this study was to analyze whether interference with the Hedgehog signaling (Hh) pathway or combined Hh/Notch blockade using small-molecule inhibitors can efficiently target these cancer stem cells and sensitize them to therapy. Using tumor sphere lines and primary patient-derived glioma cultures we demonstrate that the Hh pathway inhibitor GANT61 (GANT) and the arsenic trioxide (ATO)-mediated Hh/Notch inhibition are capable to synergistically induce cell death in combination with the natural anticancer agent (-)-Gossypol (Gos). Only ATO in combination with Gos also strongly decreased stemness marker expression and prevented sphere formation and recovery. These synergistic effects were associated with distinct proteomic changes indicating diminished DNA repair and markedly reduced stemness. Finally, using an organotypic brain slice transplantation model, we show that combined ATO/Gos treatment elicits strong growth inhibition or even complete elimination of tumors. Collectively, our data show for the first time that ATO and Gos, two drugs that can be used in the clinic, represent a promising targeted therapy approach for the synergistic elimination of glioma stem-like cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.