Alpha-ketoglutarate (AKG) inhibits proliferation of colon adenocarcinoma cells in normoxic conditions
(2012) In Scandinavian Journal of Gastroenterology 47(5). p.565-571- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2571543
- author
- Rzeski, Wojciech ; Walczak, Katarzyna ; Juszczak, Malgorzata ; Langner, Ewa ; Pozarowski, Piotr ; Kandefer-Szerszen, Martyna and Pierzynowski, Stefan LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- alpha-ketoglutarate, cell cycle, normoxia, p21 Waf1/Cip1, proliferation, Rb
- in
- Scandinavian Journal of Gastroenterology
- volume
- 47
- issue
- 5
- pages
- 565 - 571
- publisher
- Taylor & Francis
- external identifiers
-
- wos:000302564700009
- scopus:84859576496
- pmid:22486188
- ISSN
- 1502-7708
- DOI
- 10.3109/00365521.2012.660539
- language
- English
- LU publication?
- yes
- id
- 40251ea1-cfc2-4d54-b653-a36ee6ee61a7 (old id 2571543)
- date added to LUP
- 2016-04-01 12:56:11
- date last changed
- 2022-03-21 07:38:19
@article{40251ea1-cfc2-4d54-b653-a36ee6ee61a7,
abstract = {{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.}},
author = {{Rzeski, Wojciech and Walczak, Katarzyna and Juszczak, Malgorzata and Langner, Ewa and Pozarowski, Piotr and Kandefer-Szerszen, Martyna and Pierzynowski, Stefan}},
issn = {{1502-7708}},
keywords = {{alpha-ketoglutarate; cell cycle; normoxia; p21 Waf1/Cip1; proliferation; Rb}},
language = {{eng}},
number = {{5}},
pages = {{565--571}},
publisher = {{Taylor & Francis}},
series = {{Scandinavian Journal of Gastroenterology}},
title = {{Alpha-ketoglutarate (AKG) inhibits proliferation of colon adenocarcinoma cells in normoxic conditions}},
url = {{http://dx.doi.org/10.3109/00365521.2012.660539}},
doi = {{10.3109/00365521.2012.660539}},
volume = {{47}},
year = {{2012}},
}