Survivin as a potential therapeutic target of acetylsalicylic acid in pituitary adenomas

Oncotarget
Kinga NémethHenriett Butz

Abstract

Acetylsalicylic acid (ASA) is known as a cancer preventing agent, but there is no data available regarding the effect of ASA on pituitary cells. We investigated 66 nonfunctioning (NFPA) and growth hormone (GH)-producing adenomas and 15 normal pituitary samples. Functional assays (cell viability, proliferation, flow cytometry cell cycle analysis, caspase-3 activation and DNA degradation) were applied to explore the effect of ASA, YM155 (survivin inhibitor), survivin-targeting siRNA and TNF-related apoptosis-inducing ligand (TRAIL) in RC-4B/C and GH3 cells. Pituitary adenoma xenografts were generated in immunocompromised mice. We found that survivin was overexpressed and TRAIL was downregulated in NFPAs compared to normal pituitary tissue. ASA decreased proliferation but did not induce apoptosis in pituitary cells. Additionally, ASA treatment decreased cells in S phase and increased cells in G2/M phase of the cell cycle. Inhibition of survivin using an inhibitor or siRNA-mediated silencing reversed the ASA-induced growth inhibition partially. In addition, we also found survivin-independent effects of ASA on the cell cycle that were mediated through inhibition of cyclin A, cyclin dependent kinase 2 (CDK2) and phospho-CDK2. We also...Continue Reading

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Citations

Jul 31, 2019·Oncotarget·Fabio Rotondo, Kalman Kovacs
Jul 25, 2019·Pathology Oncology Research : POR·Raffaella Mormile

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Methods Mentioned

BETA
xenograft
flow cytometry
transfection
xenografts
coronary artery surgery
Low
PCR
Protein Assay

Software Mentioned

Image J
Quant 7
GraphPad
ModFit
CaseViewer
Cell Quest Pro
GraphPad Prism
NuclearQuant

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis