{
  "abstract": "Background/Objectives: Glioblastoma exhibits profound therapy resistance driven in part by complex pro-survival signaling. We hypothesized that targeting lipid metabolism via SREBP-1/2 inhibition (fatostatin) might alter the apoptotic phenotype and facilitate an apoptotic response driven by BH3 mimetics (ABT-263) in glioblastoma in vitro. Methods: Dynamic BH3 profiling was performed to detect apoptotic priming. The combined inhibition of SREBP-1/2 and Bcl-xL/Bcl-2 was evaluated across 2- and 3-dimensional culture models. The cell lines used included established cell lines as well as primary cultures and glioma stem-like cells. Extracellular flux analysis was used to assess metabolic effects. Changes in migration were evaluated through time-lapse analysis, scratch, and Transwell assays. Results: BH3 profiling showed that treatment with fatostatin increased Bcl-xL/Bcl-2 reliance, while ABT-263 increased Mcl-1 dependence. The combination showed potent synergy in inhibiting viability and spheroid growth, driven at least in part by enhanced caspase-dependent apoptosis. Mechanistically, fatostatin induced dose-dependent Mcl-1 downregulation, sensitizing cells to ABT-263. Dual treatment suppressed oxidative phosphorylation and impaired cell migration, while exhibiting low toxicity in non-pathological cells. Conclusions: This study indicates that combined inhibition of SREBP-1/2 and Bcl-xL/Bcl-2 represents a promising therapeutic strategy for the treatment of glioblastoma. The efficacy of this dual approach potentially lies in the downregulation of Mcl-1 induced by fatostatin and suppression of oxidative phosphorylation. Further studies are warranted.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurosurgery, Ulm University Medical Center, 89081 Ulm, Germany.",
    "Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University Medical Center Regensburg, 93053 Regensburg, Germany.",
    "Institute of Neurogenetics, University of Lübeck, 23562 Lübeck, Germany.",
    "Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, 89081 Ulm, Germany.",
    "Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Davide Tosin",
      "orcid": "0009-0007-5968-1110"
    },
    {
      "affs": [
        1
      ],
      "name": "Felix Seyfried",
      "orcid": "0000-0003-3738-3001"
    },
    {
      "affs": [
        0
      ],
      "name": "Annika Hajosch"
    },
    {
      "affs": [
        0
      ],
      "name": "Dominik Schlotter"
    },
    {
      "affs": [
        2
      ],
      "name": "Letizia Santinelli",
      "orcid": "0009-0009-9220-0547"
    },
    {
      "affs": [
        3
      ],
      "name": "Mike-Andrew Westhoff",
      "orcid": "0000-0003-3256-7100"
    },
    {
      "affs": [
        4
      ],
      "name": "Markus Siegelin"
    },
    {
      "affs": [
        0
      ],
      "name": "Christian Rainer Wirtz",
      "orcid": "0000-0001-8358-1813"
    },
    {
      "affs": [
        0
      ],
      "name": "Georg Karpel-Massler",
      "orcid": "0000-0001-8236-5369"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6ppvh6e6w2web.bib",
  "cited_by": 0,
  "doi": "10.3390/pharmaceutics18101327",
  "fulltext_url": "https://europepmc.org/articles/PMC13708444",
  "id": "6ppvh6e6w2web",
  "issns": [
    "1999-4923"
  ],
  "landing_url": "https://europepmc.org/article/MED/42942857",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Cell death mechanisms and regulation"
    ]
  ],
  "openalex": "W7223018625",
  "pdf_url": "https://europepmc.org/articles/PMC13708444?pdf=render",
  "pmcid": "PMC13708444",
  "pmid": "42942857",
  "published": "2026-10-20",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6ppvh6e6w2web.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42942857",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42942857"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Cell death mechanisms and regulation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "BH3 Profiling Identifies Apoptotic Priming by SREBP-1/-2 Inhibition and Synergistic Anti-Glioblastoma Activity When Combined with ABT-263 In Vitro.",
  "title_text": "BH3 Profiling Identifies Apoptotic Priming by SREBP-1/-2 Inhibition and Synergistic Anti-Glioblastoma Activity When Combined with ABT-263 In Vitro.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:12Z",
  "url": "https://research.draconitic.com/paper/6ppvh6e6w2web",
  "venue": "Pharmaceutics",
  "versions": []
}