Atiprimod induce apoptosis in pituitary adenoma: Endoplasmic reticulum stress and autophagy pathways
![Thumbnail](/xmlui/themes/Mirage2//images/restricted.png)
Göster/ Aç
Erişim
info:eu-repo/semantics/embargoedAccessTarih
2019Yazar
Çöker Gürkan, AjdaAyhan Şahin, Burcu
Keçeloğlu, Gizem
Obakan Yerlikaya, Pınar
Arısan, Elif Damla
Palavan Ünsal, Narçın
Üst veri
Tüm öğe kaydını gösterKünye
Çöker 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.29281Özet
Pituitary 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.
WoS Q Kategorisi
Q2Scopus Q Kategorisi
Q2Kaynak
Journal of Cellular BiochemistryCilt
120Sayı
12Koleksiyonlar
- Makale Koleksiyonu [3790]
- PubMed İndeksli Yayınlar Koleksiyonu [4251]
- Scopus İndeksli Yayınlar Koleksiyonu [6601]
- WoS İndeksli Yayınlar Koleksiyonu [6677]