Pharmacologic activation of PKM2 slows lung tumor xenograft growth
| Autor: | Anna Senina, David Vollmer, Xiao-Hui Liu, Kevin Wright, Virgil McCarthy, Scott Pearce, Marc O'Reilly, Jason M. Foulks, K. Mark Parnell, Steven B. Kanner, Jihua Liu, Bai Luo, Jeremy Bullough, Koc-Kan Ho, Adrianne Clifford, Rebecca N. Nix, Michael Saunders, Yong Xu, Michael V. McCullar |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Cancer Research Benzylamines Thyroid Hormones Lung Neoplasms Cell Survival Molecular Conformation PKM2 Biology Enzyme activator Mice In vivo Cell Line Tumor medicine Animals Humans Dose-Response Relationship Drug Cancer Membrane Proteins medicine.disease Xenograft Model Antitumor Assays In vitro Tumor Burden Enzyme Activation Disease Models Animal Oncology Cell culture Cancer cell Cancer research Adenocarcinoma Pyrazoles Female Carrier Proteins Protein Binding |
| Zdroj: | Molecular cancer therapeutics. 12(8) |
| ISSN: | 1538-8514 |
| Popis: | Inactivation of the M2 form of pyruvate kinase (PKM2) in cancer cells is associated with increased tumorigenicity. To test the hypothesis that tumor growth may be inhibited through the PKM2 pathway, we generated a series of small-molecule PKM2 activators. The compounds exhibited low nanomolar activity in both biochemical and cell-based PKM2 activity assays. These compounds did not affect the growth of cancer cell lines under normal conditions in vitro, but strongly inhibited the proliferation of multiple lung cancer cell lines when serine was absent from the cell culture media. In addition, PKM2 activators inhibited the growth of an aggressive lung adenocarcinoma xenograft. These findings show that PKM2 activation by small molecules influences the growth of cancer cells in vitro and in vivo, and suggest that such compounds may augment cancer therapies. Mol Cancer Ther; 12(8); 1453–60. ©2013 AACR. |
| Databáze: | OpenAIRE |
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