Purvalanol A is a strong apoptotic inducer via activating polyamine catabolic pathway in MCF-7 estrogen receptor positive breast cancer cells
| Autor: | Narcin Palavan-Unsal, Pinar Obakan, Ajda Coker-Gurkan, Elif Damla Arisan, Pelin Ozfiliz |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cell Survival
Spermine Down-Regulation Antineoplastic Agents Breast Neoplasms Apoptosis Therapeutics Biology chemistry.chemical_compound Breast cancer Acetyltransferases Cyclin-dependent kinase Genetics Polyamines Roscovitine Humans Bcl-2 Disease Enzyme Inhibitors Phosphorylation Molecular Biology Purvalanol A Oxidoreductases Acting on CH-NH Group Donors Inhibitors General Medicine Agents Mitochondria Up-Regulation Cell biology Spermidine Receptors Estrogen chemistry Caspase-3 Purines Cancer cell MCF-7 Cells Cancer research biology.protein Polyamine homeostasis Female Drug Screening Assays Antitumor Polyamine Oxidase Polyamine oxidase Metabolic Networks and Pathways CDK inhibitor |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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