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Purvalanol induces endoplasmic reticulum stress-mediated apoptosis and autophagy in a time-dependent manner in HCT116 colon cancer cells

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Author
Çoker Gürkan, Ajda
Arısan, Elif Damla
Obakan Yerlikaya, Pınar
Akalın, Kübra
Özbey, Utku
Palavan Ünsal, Zeynep Narçın
Type
Article
Date
2015-06
Language
en_US
Metadata
Show full item record
Abstract
Purvalanol, a novel cyclin-dependent kinase inhibitor, is referred to as a strong apoptotic inducer which causes cell cycle arrest in various cancer cells such as prostate, breast and colon cancer cell lines. Various physiological and pathological conditions such as glucose starvation, inhibition of protein glycosylation and oxidative stress may cause an accumulation of unfolded proteins in the endoplasmic reticulum (ER), leading to the unfolded protein response (UPR) and autophagy. Lacking proteosomal function on aggregates of unfolded proteins, ER stress may induce autophagic machinery. Autophagy, an evolutionarily conserved process, is characterized by massive degradation of cytosolic contents. In the present study, our aim was to determine the time-dependent, ER-mediated apoptotic and autophagy induction of purvalanol in HCT 116 colon cancer cells. Fifteen micromoles of purvalanol induced a reduction in cell viability by 20 and 35% within 24 and 48 h, respectively. HCT 116 colon cancer cells were exposed to purvalanol, which activated ER stress via upregulation of PERK, IREl alpha gene expression, eIF-2 alpha phosphorylation and ATF-6 cleavage at early time-points in the HCT 116 colon cancer cells. Moreover, we determined that during purvalanol-mediated ER stress, autophagic machinery was also activated prior to apoptotic cell death finalization. Beclin-1 and Atg-5 expression levels were upregulated and LC3 was cleaved after a 6 h purvalanol treatment. Purvalanol induced mitochondrial membrane potential loss, caspase-7 and caspase-3 activation and PARP cleavage following a 48 h treatment. Thus, we conclude that the anticancer effect of purvalanol in HCT 116 cells was due to ER stress-mediated apoptosis; however, purvalanol triggered autophagy, which functions as a cell survival mechanism at early time-points.
Subject
Purvalanol
 Endoplasmic Reticulum stress; 
Autophagy
Apoptosis
Colon Cancer
Unfolded protein response
Polyamine catabolic pathway
Transcription factors
Carcinoma cells
Er stress
Inhibitors
Induction
Kinases
Chop
Calreticulin
URI
https://doi.org/10.3892/or.2015.3918
https://hdl.handle.net/11413/2074
Collections
  • Makaleler / Articles [140]
  • Pubmed Publications [149]
  • Scopus Publications [724]
  • WoS Publications [1016]

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İstanbul Kültür University

Hakkında |Politika | Kütüphane | İletişim | Send Feedback | Admin

Istanbul Kültür University, Ataköy Campus E5 Karayolu Üzeri Bakırköy 34158, İstanbul / TURKEY
Copyright © İstanbul Kültür University

Creative Commons Lisansı
IKU Institutional Repository, Creative Commons Alıntı-GayriTicari-Türetilemez 4.0 Uluslararası Lisansı ile lisanslanmıştır.

Designed by  UNIREPOS