Chronic administration of metformin exerts cytostatic and cytotoxic effects via the PP2A-GSK3β-MCL-1 pathway by inhibiting the tmCLIC1 membrane protein in glioblastoma-initiating cells
The therapeutic role of metformin to treat brain tumors remains debated. Our findings show that drug delivery is essential, as in vivo, tumor growth decreases at concentrations below 10 nanomolar. We propose that sustained CNS metformin levels may improve tmCLIC1 inhibition, providing a basis for optimizing interactions with metformin or related compounds to enhance therapeutic efficacy.
Authors
- Beatrice Balboni (ORCID: https://orcid.org/0000-0002-2729-4235)
- Michele Mazzanti (ORCID: https://orcid.org/0000-0002-1819-3811)
- Stefania Girotto (ORCID: https://orcid.org/0000-0002-0339-6675)
- Andrea Cavalli (ORCID: https://orcid.org/0000-0002-6370-1176)
- Luca Palloni (ORCID: https://orcid.org/0000-0002-9004-4415)
- Saverio Minucci (ORCID: https://orcid.org/0000-0001-5678-536X)
- Marina Veronesi (ORCID: https://orcid.org/0000-0001-8491-8844)
- Tullio Florio (ORCID: https://orcid.org/0000-0002-2394-996X)
- Massimo Pasqualetti (ORCID: https://orcid.org/0000-0002-0844-8139)
- Gaetano Cannavale
- Sara Baldassari (ORCID: https://orcid.org/0000-0003-4602-6954)
- Alessandro Fantin (ORCID: https://orcid.org/0000-0002-5517-6068)
- Carlo Camilloni (ORCID: https://orcid.org/0000-0002-9923-8590)
- Francesca Cianci (ORCID: https://orcid.org/0000-0002-9935-1526)
- Riccardo Cazzoli (ORCID: https://orcid.org/0000-0003-2813-3510)
- Carlotta Tacconi (ORCID: https://orcid.org/0000-0002-6431-7555)
- Noemi Barsotti (ORCID: https://orcid.org/0000-0002-6399-436X)
- Gabriele Caviglioli (ORCID: https://orcid.org/0000-0001-8129-7421)
- Federico Ballabio (ORCID: https://orcid.org/0000-0001-5702-3674)
- Giorgia Ailuno (ORCID: https://orcid.org/0000-0002-2234-1805)
- Federica Barbieri (ORCID: https://orcid.org/0000-0001-8988-6896)
- Ivan Verduci (ORCID: https://orcid.org/0000-0002-2238-3546)
- Matteo Ranucci (ORCID: https://orcid.org/0000-0003-3332-6202)
- Alice Balboni (ORCID: https://orcid.org/0009-0006-9809-5715)
- Guido Rey (ORCID: https://orcid.org/0009-0009-9060-541X)
Institutions
- University of Pisa (IT)
- Vita-Salute San Raffaele University (IT)
- University of Milan (IT)
- University of Zurich (CH)
- Italian Institute of Technology (IT)
- UNSW Sydney (AU)
- Ospedale Policlinico San Martino (IT)
- European Institute of Oncology (IT)
- University of Genoa (IT)
Publication Details
- Journal
- Journal of Experimental & Clinical Cancer Research
- Published
- 2025-11-24
- DOI
- https://doi.org/10.1186/s13046-025-03577-3
- Citations
- 1
- Primary Topic
- Metabolism, Diabetes, and Cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Università degli Studi di Milano