ArticleJournal of experimental & clinical cancer research : CR2019
The kinase inhibitor SI113 induces autophagy and synergizes with quinacrine in hindering the growth of human glioblastoma multiforme cells.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Time-Dependent Effects of Cisplatin on Autophagy Gene Expression in Bladder Cancer Cells.Biomedicines · 2026Article
- Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain.Experimental neurology · 2024Review
- Chlorpromazine affects glioblastoma bioenergetics by interfering with pyruvate kinase M2.Cell death & disease · 2023Article
- SGK1, a Critical Regulator of Immune Modulation and Fibrosis and a Potential Therapeutic Target in Chronic Graft-Versus-Host Disease.Frontiers in immunology · 2022Review
- Diagnostic and prognostic potential of the proteomic profiling of serum-derived extracellular vesicles in prostate cancer.Cell death & disease · 2021Article
- Review
- Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma ProliferationFrontiers in oncology · 2021Article
- Synthesis and Antibacterial Evaluation of New Pyrazolo[3,4-Molecules (Basel, Switzerland) · 2020Article
- Targeting tumor hypoxia and mitochondrial metabolism with anti-parasitic drugs to improve radiation response in high-grade gliomas.Journal of experimental & clinical cancer research : CR · 2020Review
- The U2AF2 /circRNA ARF1/miR-342-3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells.Journal of experimental & clinical cancer research : CR · 2020Article
- Development of Pyrazolo[3,4-ACS medicinal chemistry letters · 2020Article
- Drug repurposing against COVID-19: focus on anticancer agents.Journal of experimental & clinical cancer research : CR · 2020Review
- SGK1 in Human Cancer: Emerging Roles and Mechanisms.Frontiers in oncology · 2020Review
- The Emerging Role of SGK1 (Serum- and Glucocorticoid-Regulated Kinase 1) in Major Depressive Disorder: Hypothesis and Mechanisms.Frontiers in genetics · 2020Review
- The prospect of serum and glucocorticoid-inducible kinase 1 (SGK1) in cancer therapy: a rising star.Therapeutic advances in medical oncology · 2020Review
- Targeting NRF2, Regulator of Antioxidant System, to Sensitize Glioblastoma Neurosphere Cells to Radiation-Induced Oxidative Stress.Oxidative medicine and cellular longevity · 2020Article
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundGlioblastoma multiforme (GBM), due to its location, aggressiveness, heterogeneity and infiltrative growth, is characterized by an exceptionally dismal clinical outcome. The small molecule SI113, recently identified as a SGK1 inhibitor, has proven to be effective in restraining GBM growth in vitro and in vivo, showing also encouraging results when employed in combination with other antineoplastic drugs or radiotherapy. Our aim was to explore the pharmacological features of SI113 in GBM cells in order to elucidate the pivotal molecular pathways affected by the drug. Such knowledge would be of invaluable help in conceiving a rational offensive toward GBM.
methodsWe employed GBM cell lines, either established or primary (neurospheres), and used a Reverse-Phase Protein Arrays (RPPA) platform to assess the effect of SI113 upon 114 protein factors whose post-translational modifications are associated with activation or repression of specific signal transduction cascades.
resultsSI113 strongly affected the PI3K/mTOR pathway, evoking a pro-survival autophagic response in neurospheres. These results suggested the use of SI113 coupled, for maximum efficiency, with autophagy inhibitors. Indeed, the association of SI113 with an autophagy inhibitor, the antimalarial drug quinacrine, induced a strong synergistic effect in inhibiting GBM growth properties in all the cells tested, including neurospheres.
conclusionsRPPA clearly identified the molecular pathways influenced by SI113 in GBM cells, highlighting their vulnerability when the drug was administered in association with autophagy inhibitors, providing a strong molecular rationale for testing SI113 in clinical trials in associative GBM therapy.
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Registered trials
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