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Epibrassinolide alters PI3K/MAPK signaling axis via activating Foxo3a-induced mitochondria-mediated apoptosis in colon cancer cells

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Author
Coşkun, Deniz
Obakan Yerlikaya, Pınar
Arısan, Elif Damla
Çoker Gürkan, Ajda
Palavan Unsal, Narcin
Type
Article
Date
2015-10-15
Language
en_US
Metadata
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Abstract
Epibrassinolide (EBR), a steroid-derived plant growth regulator, has been recently suggested as an apoptotic inducer in different cancer cells. In this experimental study, we investigated the potential apoptotic effect of EBR on stress-related and survival signaling molecules in colon carcinoma cells. EBR decreased cell viability and colony formation in HCT 116 and HT-29 colon carcinoma cells. The inactivation of PI3K/AKT by EBR treatment led to upregulation of Foxo3a, which in turn induced apoptosis in HCT 116 and HT-29 cells. In addition, the upstream non-receptor protein tyrosine kinase Src was found elevated allowing to the upregulation of p38, stress-activated protein kinase/Jun amino-terminal kinase and extracellular signal-regulated kinase 1/2 and their target genes c-jun, c-fos and c-myc in a time-dependent manner in HCT 116 cells within 48 h. The alterations in PA metabolism caused intracellular PA pool decrease. The upregulation of pro-apoptotic Bak, Bax, Puma and Bim were accompanied with the decrease in Mcl-1 in HCT 116 and Bcl-x(L), expression profiles in HT-29 following 48 h EBR treatment. We suggest that the upregulation of Bim expression levels might be related with one of the PI3K/AKT target transcription factor Foxo3a, which was dephosphorylated by EBR treatment in HCT 116 and HT-29 cells. (C) 2015 Elsevier Inc. All rights reserved.
Subject
Epibrassinolide
Polyamines
Apoptosis
Colon cancer
PI3K
AKT
Foxo3a
Forkhead Transcription Factor
Polyamine Catabolism
Cycle Arrest
Map Kinases
Pathways
Jnk
P53
Brassinosteroids
Inhibition
Expression
URI
https://doi.org/10.1016/j.yexcr.2015.08.015
https://hdl.handle.net/11413/2023
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  • 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