AT-101 acts as anti-proliferative and hormone suppressive agent in mouse pituitary corticotroph tumor cells

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dc.contributor.authorYurekli, B. S.
dc.contributor.authorKaraca, B.
dc.contributor.authorKisim, A.
dc.contributor.authorBozkurt, E.
dc.contributor.authorAtmaca, H.
dc.contributor.authorCetinkalp, S.
dc.contributor.authorOzgen, G.
dc.contributor.authorYilmaz, C.
dc.contributor.authorUzunoglu, S.
dc.contributor.authorUslu, R.
dc.contributor.authorSaygili, F.
dc.date.accessioned2019-10-27T10:42:18Z
dc.date.available2019-10-27T10:42:18Z
dc.date.issued2018
dc.departmentEge Üniversitesien_US
dc.description.abstractPurpose Gossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (-)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing's disease still remains a challenge for the clinicians. We aimed to investigate the cytotoxic and apoptotic effects of AT-101 in mouse pituitary corticotroph tumor AtT20 cells. Methods Cytotoxic effect of AT-101 was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation and Caspase-3/7 activity. Changes in mRNA expressions of apoptosis-related genes were investigated by qPCR array after treatment with AT-101. ACTH was measured by ACTH-EIA Kit. Results AT-101 induced cytotoxicity and apoptosis in AtT20 cells. mRNA levels of pro-apoptotic genes such as TNFR-SF-10B, Bid, PYCARD, Caspase-8, Caspase-3, and Caspase-7 were induced by 2.0-, 1.5-, 1.7-, 1.5-, 1.6-, and 2-fold, respectively, in AtT20 cells by AT-101 treatment. Moreover, some of the anti-apoptotic genes such as BCL2L10, NAIP1, and PAK-7 were reduced by 2.1-, 2.3-, 4.0-fold, respectively, in AtT20 cells. AT-101 also decreased ACTH secretion significantly. Conclusion AT-101 induces apoptosis in mouse pituitary corticotroph tumor cells.en_US
dc.description.sponsorshipScientific Research Projects Committee of Ege UniversityEge University [2011-TIP-077]en_US
dc.description.sponsorshipThis work was supported by Scientific Research Projects Committee of Ege University (Project No: 2011-TIP-077).en_US
dc.identifier.doi10.1007/s40618-017-0733-8en_US
dc.identifier.endpage240en_US
dc.identifier.issn1720-8386
dc.identifier.issue2en_US
dc.identifier.pmid28730425en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage233en_US
dc.identifier.urihttps://doi.org/10.1007/s40618-017-0733-8
dc.identifier.urihttps://hdl.handle.net/11454/30681
dc.identifier.volume41en_US
dc.identifier.wosWOS:000423387100010en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofJournal of Endocrinological Investigationen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAT-101en_US
dc.subjectCytotoxicityen_US
dc.subjectApoptosisen_US
dc.subjectAtT20en_US
dc.subjectACTHen_US
dc.titleAT-101 acts as anti-proliferative and hormone suppressive agent in mouse pituitary corticotroph tumor cellsen_US
dc.typeArticleen_US

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