Treatment with Cyclic AMP Activators Reduces Glioblastoma Growth and Invasion as Assessed by Two-Photon Microscopy

(1) Background: Despite progress in surgery and radio-chemotherapy of glioblastoma (GB), the prognosis remains very poor. GB cells exhibit a preference for hypoxia to maintain their tumor-forming capacity. Enhancing oxidative phosphorylation-known as the anti-Warburg effect-with cyclic AMP activator...

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Published in:Cells (Basel, Switzerland) Switzerland), 2021-03, Vol.10 (3), p.556
Main Authors: Wartchow, Krista Minéia, Schmid, Benjamin, Tripal, Philipp, Stadlbauer, Andreas, Buchfelder, Michael, Gonçalves, Carlos-Alberto, Kleindienst, Andrea
Format: Article
Language:English
Subjects:
2-photon-microscopy
Brain architecture
Brain cancer
Brain slice preparation
Cell culture
Cell cycle
Cell differentiation
Cell proliferation
Cell viability
Chemotherapy
Cyclic AMP
Experiments
Fluorescence microscopy
Forskolin
Glioblastoma
Glucose
Glycerol
Growth patterns
Hypoxia
Laboratory animals
Metabolism
Microscopy
Oxidative phosphorylation
Penicillin
Phosphorylation
Surgery
treatment
Tumors
Warburg effect
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Summary:(1) Background: Despite progress in surgery and radio-chemotherapy of glioblastoma (GB), the prognosis remains very poor. GB cells exhibit a preference for hypoxia to maintain their tumor-forming capacity. Enhancing oxidative phosphorylation-known as the anti-Warburg effect-with cyclic AMP activators has been demonstrated to drive GB cells from proliferation to differentiation thereby reducing tumor growth in a cell culture approach. Here we re-evaluate this treatment in a more clinically relevant model. (2) Methods: The effect of treatment with dibutyryl cyclic AMP (dbcAMP, 1 mM) and the cAMP activator forskolin (50µM) was assessed in a GB cell line (U87GFP+, 10 cells) co-cultured with mouse organotypic brain slices providing architecture and biochemical properties of normal brain tissue. Cell viability was determined by propidium-iodide, and gross metabolic effects were excluded in the extracellular medium. Tumor growth was quantified in terms of area, volume, and invasion at the start of culture, 48 h, 7 days, and 14 days after treatment. (3) Results: The tumor area was significantly reduced following dbcAMP or forskolin treatment (F = 5.968, = 0.0029). 3D volumetric quantification utilizing two-photon fluorescence microscopy revealed that the treated tumors maintained a spheric shape while the untreated controls exhibited the GB typical invasive growth pattern. (4) Conclusions: Our data demonstrate that treatment with a cAMP analog/activator reduces GB growth and invasion.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10030556