Article
CUSP9* elicits significant anti-cancer activity against glioblastoma cells in vitro
CUSP9* hat signifikante inhibierende Wirkungen auf Glioblastomzellen in vitro
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Published: | May 8, 2019 |
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Objective: Drug repurposing is a strategy to safely accelerate the clinical application of therapeutics that provide anti-cancer activity. CUSP9* represents such a therapeutic regime which includes nine repurposed drugs along with low-dose metronomic temozolomide. In this work, we examined the biological activity of the CUSP9* regimen in an in vitro setting of glioblastoma.
Methods: MTT and soft-agar assays were used to examine cellular proliferation. Staining for Annexin V/PI and Western blotting were used to examine pro-apoptotic effects. A spheroid assay was performed to assess effects of the treatment on three-dimensional growth. Time-lapse microscopy, radius and transwell assays were performed to examine anti-migratory effects.
Results: Treatment with CUSP9* exerted profound anti-proliferative activity and inhibited anchorage-independent growth among a broad panel of established, primary cultured and glioblastoma stem-like cells. These effects were accompanied by enhanced apoptosis as indicated by an increased fraction of Annexin V-positive cells and enhanced caspase-3 cleavage. Moreover, CUSP9* led to significantly decreased 3-dimensional tumor formation. In addition, non-directed and directed movement of glioblastoma cells were significantly impaired following CUSP9* treatment.
Conclusion: se data suggest that CUSP9* has potent anti-cancer activity in vitro which is currently further explored by a clinical trial being conducted at our institution (NCT02770378).