Atiprimod induce apoptosis in pituitary adenoma: Endoplasmic reticulum stress and autophagy pathways

Basit Öğe Kaydı
dc.contributor.authorÇöker Gürkan, Ajda
dc.contributor.authorAyhan Şahin, Burcu
dc.contributor.authorKeçeloğlu, Gizem
dc.contributor.authorObakan Yerlikaya, Pınar
dc.contributor.authorArısan, Elif Damla
dc.contributor.authorPalavan Ünsal, Narçın
dc.date.accessioned2019-12-19T07:27:07Z
dc.date.available2019-12-19T07:27:07Z
dc.date.issued2019
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyokimya Ana Bilim Dalı
dc.description.abstractPituitary adenoma is the most common tumor with a high recurrence rate due to a hormone-dependent JAK/signal transducer and activator of transcriptions (STAT) signaling. Atiprimod, a novel compound belonging to the azaspirane class of cationic amphiphilic drugs, has antiproliferative, anticarcinogenic effects in multiple myeloma, breast, and hepatocellular carcinoma by blocking STAT3 activation. Therapeutic agents' efficiency depends on endoplasmic reticulum (ER) stress-autophagy regulation during drug-mediated apoptotic cell death decision. However, the molecular machinery of dose-dependent atiprimod treatment regarding ER stress-autophagy has not been investigated yet. Thus, our aim is to investigate the ER stress-autophagy axis in atiprimod-mediated apoptotic cell death in GH-secreting rat cell line (GH3) pituitary adenoma cells. Dose-dependent atiprimod treatment decreased GH3 cell viability, inhibited cell growth, and colony formation. Upregulation of Atg5, Atg12, Beclin-1 expressions, cleavage of LC-3II and formation of autophagy vacuoles were determined only after 1 mu M atiprimod exposure. In addition, atiprimod-triggered ER stress was evaluated by BiP, C/EBP-homologous protein (CHOP), p-PERK upregulation, and Ca+2 release after 1 mu M atiprimod exposure. Concomitantly, increasing concentration of atiprimod induced caspase-dependent apoptotic cell death via modulating Bcl(2) family members. Moreover, by N-acetyl cycteinc pretreatment, atiprimod triggered reactive oxygen species generation and prevented apoptotic induction. Concomitantly, dose-dependent atiprimod treatment decreased both GH and STAT3 expression in GH3 cells. In addition, overexpression of STAT3 increased atiprimod-mediated cell viability loss and apoptotic cell death through suppressing autophagy and ER stress key molecules expression profile. In conclusion, a low dose of atiprimod exposure triggers autophagy and mild-ER stress as a survival mechanism, but increased atiprimod dose induced caspase-dependent apoptotic cell death by targeting STAT3 in GH3 pituitary adenoma cells.
dc.identifier.citationÇöker Gürkan, A., Ayhan Şahin, B., Keçeloğlu, G., Obakan Yerlikaya, P., Arısan, E.D. ve Palavan Ünsal, N. (2019). Atiprimod induce apoptosis in pituitary adenoma: Endoplasmic reticulum stress and autophagy pathways. Journal of Cellular Biochemistry. 120(12), 19749-19763. https://doi.org/10.1002/jcb.29281
dc.identifier.doi10.1002/jcb.29281
dc.identifier.endpage19763
dc.identifier.issn1097-4644
dc.identifier.issn0730-2312
dc.identifier.issue12
dc.identifier.scopusqualityQ2
dc.identifier.startpage19749
dc.identifier.urihttps://doi.org/10.1002/jcb.29281
dc.identifier.urihttps://hdl.handle.net/20.500.12511/4534
dc.identifier.volume120
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofJournal of Cellular Biochemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectApoptotic Cell Death
dc.subjectAtiprimod
dc.subjectAutophagy
dc.subjectEndoplasmic Reticulum
dc.subjectGH3 Cells
dc.titleAtiprimod induce apoptosis in pituitary adenoma: Endoplasmic reticulum stress and autophagy pathways
dc.typeArticle

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Küçük Resim Yok
İsim:
keceloglu-gizem(2019).pdf
Boyut:
2.94 MB
Biçim:
Adobe Portable Document Format
Açıklama:
Tam Metin / Full Text
İndir
Lisans paketi
Listeleniyor 1 - 1 / 1
Küçük Resim Yok
İsim:
license.txt
Boyut:
1.44 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

Scopus İndeksli Yayınlar Koleksiyonu
Makale Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu