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Cells
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The Pivotal Role of Tumor Stem Cells in Glioblastoma: Second...
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The Pivotal Role of Tumor Stem Cells in Glioblastoma: Second Edition

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 28 February 2026 | Viewed by 132

Special Issue Editors

Dr. Paola Palumbo

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Guest Editor
Department of Life, Health & Environmental Sciences, University of L’Aquila, Via Pompeo Spennati, Building Rita Levi Montalcini, 67100 L’Aquila, Italy
Interests: inflammation; glioma; cancer stem cells; tumor biology; cyclooxygenase-2; nitric oxide synthase 2
Special Issues, Collections and Topics in MDPI journals
Dr. Silvano J. Santini

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Guest Editor
Department of Life, Health & Environmental Sciences, University of L’Aquila, Via Pompeo Spennati, Building “Rita Levi Montalcini”, 67100 L’Aquila, Italy
Interests: dicarbonyl stress; oxidative stress; mitochondrial metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are delighted to announce the launch of a Special Issue of Cells on all aspects related to the theme of “The Pivotal Role of Tumor Stem Cells in Glioblastoma: Second Edition”. We invite you to contribute original research articles or reviews to share your cutting-edge research, insights, and innovation on new mechanistic, functional, cellular, biochemical, or general evidence of cancer stem cells in glioblastoma.

Glioblastoma is one of the most complex, fast-growing, aggressive, and treatment-resistant cancers with an extremely poor prognosis. The latest therapeutic approaches are often ineffective due to the presence of glioblastoma stem cells (GSCs), which play a crucial role in resistance and recurrence.

GSCs can also significantly impact the tumor microenvironment, influencing the fate of all neighboring resident cells through genetic reprogramming and inducing key stemness features. The precise molecular mechanisms underlying the intricate scenario of GSC are not yet fully understood. A deeper understanding of the GSCs' molecular and biological features could certainly enable us to define new, targeted, and more effective therapeutic approaches to overcome cancer resistance, thereby improving survival rates and treatment responses.

Dr. Paola Palumbo
Dr. Silvano J. Santini
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glioblastoma stem cells
  • resistance
  • cancer therapy
  • signaling pathways
  • tumor microenvironment

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Published Papers (1 paper)

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Research

21 pages, 5080 KB  
Article
Apigenin Induces Autophagy and Apoptosis in Chemoresistant Glioblastoma Cells and Inhibits Tumorigenicity Associated with Regulation of Immunomodulatory Proteins and Glial Cells Response
by Paulo Lucas Cerqueira Coelho, Cleonice Creusa dos Santos, Alessandra Bispo da Silva, Karina Costa da Silva, Monique Reis de Santana, Balbino Lino dos Santos, Giselle Pinto de Faria Lopes, Marie Pierre Junier, Hervé Chneiweiss, Vivaldo Moura-Neto, Maria de Fátima Dias Costa, Suzana Braga-de-Souza and Silvia Lima Costa
Cells 2025, 14(19), 1552; https://doi.org/10.3390/cells14191552 - 3 Oct 2025
Abstract
Background: Glioblastomas (GBMs) are the most aggressive and common neoplasms that affect glial cells, presenting rapid growth, invasion, and resistance to treatments. Studies have demonstrated the potentially inhibitory effect of flavonoids on glioblastoma cells’ stemness and viability. However, further research is needed to [...] Read more.
Background: Glioblastomas (GBMs) are the most aggressive and common neoplasms that affect glial cells, presenting rapid growth, invasion, and resistance to treatments. Studies have demonstrated the potentially inhibitory effect of flavonoids on glioblastoma cells’ stemness and viability. However, further research is needed to explore sensitivity and the mechanism of action in chemoresistant cells. Methods: In this study, we characterized the impact of apigenin treatment on the viability and differentiation of human GBM cells in vitro and its effects on tumorigenesis and regulation of the inflammatory response in vivo. Results: The flavonoid apigenin reduced the viability of U-251 cells, patient-derived cells TG-1 and OB-1 stem cells in a dose-dependent manner, associated with the induction of acidic vesicle organelles formation and apoptosis. Treatment with apigenin also inhibited migration and induced neural differentiation in the remaining viable cells, characterized by a decrease in the expression of the precursor marker nestin and an increase in the expression of astrocyte and neuron markers, GFAP and β-III tubulin, respectively. The xenotransplantation of apigenin-pretreated U251 cells into rat brains did not lead to tumor formation, unlike untreated cells. The surrounding area of transplanted untreated U251 cells exhibited reactive microglia and astrocytes, along with increased VEGF expression, which was absent in implant sites of apigenin-pretreated GBM cells. Moreover, in this implant area, we observed a significant decrease in the expression of mRNA for inflammatory factors IL-1β, TNF, and NOS2, and the downregulation of IL-10 and IL-4. Conclusions: These results demonstrate that apigenin inhibits the growth of tumoral cells, affecting the viability of tumor stem cells and impairing tumorigenicity, while altering the regulatory profile of immunomodulatory proteins. Therefore, this flavonoid can be considered for further studies to determine its use as an adjuvant to the treatment of human GBMs. Full article
(This article belongs to the Special Issue The Pivotal Role of Tumor Stem Cells in Glioblastoma: Second Edition)
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