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Purvalanol A is a strong apoptotic inducer via activating polyamine catabolic pathway in MCF-7 estrogen receptor positive breast cancer cells

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Author
Obakan, Pınar
Arısan, Elif Damla
Özfiliz Kılbaş, Pelin
Çoker Gürkan, Ajda
Palavan Unsal, Narçin
Type
Article
Date
2014
Language
en_US
Metadata
Show full item record
Abstract
Purvalanol A is a specific CDK inhibitor which triggers apoptosis by causing cell cycle arrest in cancer cells. Although it has strong apoptotic potential, the mechanistic action of Purvalanol A on significant cell signaling targets has not been clarified yet. Polyamines are crucial metabolic regulators affected by CDK inhibition because of their role in cell cycle progress as well. In addition, malignant cells possess impaired polyamine homeostasis with high level of intracellular polyamines. Especially induction of polyamine catabolic enzymes spermidine/spermine N1-acetyltransferase (SSAT), polyamine oxidase (PAO) and spermine oxidase (SMO) induced toxic by-products in correlation with the induction of apoptosis in cancer cells. In this study, we showed that Purvalanol A induced apoptosis in caspase- dependent manner in MCF-7 ER(+) cells, while MDA-MB-231 (ER-) cells were less sensitive against drug. In addition Bcl-2 is a critical target for Purvalanol A, since Bcl-2 overexpressed cells are more resistant to Purvalanol A-mediated apoptosis. Furthermore, exposure of MCF-7 cells to Purvalanol A triggered SSAT and PAO upregulation and the presence of PAO/SMO inhibitor, MDL 72,527 prevented Purvalanol A-induced apoptosis.
Subject
Polyamines
Apoptosis
Purvalanol A
Breast cancer
Bcl-2
Down-Regulation
Roscovitine
Inhibitors
Agents
Phosphorylation
Therapeutics
Caspase-3
Spermine
Disease
Oxidase
URI
https://doi.org/10.1007/s11033-013-2847-1
https://hdl.handle.net/11413/2063
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