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Alpha-ketoglutarate (AKG) inhibits proliferation of colon adenocarcinoma cells in normoxic conditions

På svenska

Author

  • Wojciech Rzeski
  • Katarzyna Walczak
  • Malgorzata Juszczak
  • Ewa Langner
  • Piotr Pozarowski
  • Martyna Kandefer-Szerszen
  • Stefan Pierzynowski

Summary, in English

Background and objective. Alpha-ketoglutarate (AKG), a key intermediate in Krebs cycle, is an important biological compound involved in the formation of amino acids, nitrogen transport, and oxidation reactions. AKG is already commercially available as a dietary supplement and its supplementation with glutamine, arginine, or ornithine alpha-ketoglutarate has been recently considered to improve anticancer immune functions. It is well documented that AKG treatment of Hep3B hepatoma cells in hypoxia induced HIF-alpha (hypoxia-inducible factor) degradation and reduced vascular endothelial growth factor (VEGF) synthesis. Moreover, AKG showed potent antitumor effects in murine tumor xenograft model, inhibiting tumor growth, angiogenesis, and VEGF gene expression. However, the mechanisms of its anticancer activity in normoxia have not been examined so far. Results. Here, we report that in normoxia, AKG inhibited proliferation of colon adenocarcinoma cell lines: Caco-2, HT-29, and LS-180, representing different stages of colon carcinogenesis. Furthermore, AKG influenced the cell cycle, enhancing the expression of the inhibitors of cyclin-dependent kinases p21 Waf1/Cip1 and p27 Kip1. Moreover, expression of cyclin D1, required in G1/S transmission, was decreased, which accompanied with the significant increase in cell number in G1 phase. AKG affected also one the key cell cycle regulator, Rb, and reduced its activation status. Conclusion. In this study for the first time, the antiproliferative activity of AKG on colon adenocarcinoma Caco-2, HT-29, and LS-180 cells in normoxic conditions was revealed. Taking into consideration an anticancer activity both in hypoxic and normoxic conditions, AKG may be considered as a new potent chemopreventive agent.

Department/s

Publishing year

2012

Language

English

Pages

565-571

Publication/Series

Scandinavian Journal of Gastroenterology

Volume

47

Issue

5

Document type

Journal article

Publisher

Taylor & Francis

Topic

  • Gastroenterology and Hepatology

Keywords

  • alpha-ketoglutarate
  • cell cycle
  • normoxia
  • p21 Waf1/Cip1
  • proliferation
  • Rb

Status

Published

ISBN/ISSN/Other

  • ISSN: 1502-7708