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

Wartchow KM, Schmid B, Tripal P, Stadlbauer A, Buchfelder M, Goncalves CA, Kleindienst A (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Cells MDPI

Book Volume: 10

Journal Issue: 3

DOI: 10.3390/cells10030556

Abstract

(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+, 104 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 (F2,249 = 5.968, p = 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.

Authors with CRIS profile

Benjamin Schmid Optical Imaging Center Erlangen (OICE) Philipp Tripal Optical Imaging Center Erlangen (OICE) Andreas Stadlbauer Department of Neurosurgery Michael Buchfelder Lehrstuhl für Neurochirurgie Andrea Kleindienst Department of Neurosurgery

Involved external institutions

Universidade Federal do Rio Grande do Sul (UFRGS) BR Brazil (BR)

How to cite

APA:

Wartchow, K.M., Schmid, B., Tripal, P., Stadlbauer, A., Buchfelder, M., Goncalves, C.-A., & Kleindienst, A. (2021). Treatment with Cyclic AMP Activators Reduces Glioblastoma Growth and Invasion as Assessed by Two-Photon Microscopy. Cells, 10(3). https://dx.doi.org/10.3390/cells10030556

MLA:

Wartchow, Krista Mineia, et al. "Treatment with Cyclic AMP Activators Reduces Glioblastoma Growth and Invasion as Assessed by Two-Photon Microscopy." Cells 10.3 (2021).

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