dc.contributor.author | Németh, K | en_US |
dc.contributor.author | Szücs, N | en_US |
dc.contributor.author | Czirják, S | en_US |
dc.contributor.author | Reiniger, L | en_US |
dc.contributor.author | Szabó, B | en_US |
dc.contributor.author | Barna, G | en_US |
dc.contributor.author | Karászi, K | en_US |
dc.contributor.author | Igaz, P | en_US |
dc.contributor.author | Zivkovic, V | en_US |
dc.contributor.author | Korbonits, M | en_US |
dc.contributor.author | Patócs, A | en_US |
dc.contributor.author | Butz, H | en_US |
dc.date.accessioned | 2018-08-14T12:48:57Z | |
dc.date.available | 2018-06-04 | en_US |
dc.date.issued | 2018-06-26 | en_US |
dc.date.submitted | 2018-07-19T06:47:20.155Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/43423 | |
dc.description.abstract | ©Németh et al. 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 aimed to test the effect of acetylsalicylic acid in an animal model using RC-4 B/C cells, but in contrast to GH3 cells, RC-4 B/C cells failed to adhere and grow a xenograft. We concluded that ASA inhibited the growth of pituitary adenoma cells. Survivin inhibition is a key mechanism explaining its antineoplastic effects. Our results suggest that inhibition of survivin with small molecules or ASA could serve as potential therapeutic agents in NFPA. | en_US |
dc.description.sponsorship | DING
This work has been funded by Hungarian Scientific
Research Grant (OTKA PD116093 to Henriett Butz) and
by Semmelweis Research-Innovation Fund (STIA-KF-17
to Henriett Butz). Attila Patocs received the “Lendulet”
grant from Hungarian Academy of Sciences. Henriett Butz
is a recipient of Bolyai Research Fellowship of Hungarian
Academy of Sciences. Kinga Németh received NTPEFÖ-P-15
grant from The Ministry of Human Capacities. | en_US |
dc.format.extent | 29180 - 29192 | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Oncotarget | en_US |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
dc.title | Survivin as a potential therapeutic target of acetylsalicylic acid in pituitary adenomas | en_US |
dc.type | Article | |
dc.rights.holder | (c) Németh et al. | |
dc.identifier.doi | 10.18632/oncotarget.25650 | en_US |
pubs.issue | 49 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 9 | en_US |
dcterms.dateAccepted | 2018-06-04 | en_US |