The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside Inhibits Cancer Cell Proliferation in Vitro and in Vivo via AMP-activated Protein Kinase
Open accessAbstract
5-Aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) is widely used as an AMP-kinase activator, which regulates energy homeostasis and response to metabolic stress. Here, we investigated the effect of AICAR, an AMPK activator, on proliferation of various cancer cells and observed that proliferation of all the examined cell lines was significantly inhibited by AICAR treatment due to arrest in S-phase accompanied with increased expression of p21, p27, and p53 proteins and inhibition of PI3K-Akt pathway. Inhibition in in vitro growth of cancer cells was mirrored in vivo with increased expression of p21, p27, and p53 and attenuation of Akt phosphorylation. Anti-proliferative effect of AICAR is mediated through activated AMP-activated protein kinase (AMPK) as iodotubericidin and dominant-negative AMPK expression vector reversed the AICAR-mediated growth arrest. Moreover, constitutive active AMPK arrested the cells in S-phase by inducing the expression of p21, p27, and p53 proteins and inhibiting Akt phosphorylation, suggesting the involvement of AMPK. AICAR inhibited proliferation in both LKB and LKB knock-out mouse embryo fibroblasts to similar extent and arrested cells at S-phase when transfected with dominant negative expression vector of LKB. Altogether, these results indicate that AICAR can be utilized as a therapeutic drug to inhibit cancer, and AMPK can be a potential target for treatment of various cancers independent of the functional tumor suppressor gene, LKB.
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Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
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LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
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Insulin and insulin-like growth factor signalling in neoplasia
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AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling
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AMPK and cell proliferation – AMPK as a therapeutic target for atherosclerosis and cancer
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Metadata
- Authors
- Rattan, R., Giri, S., Singh, A. K., & Singh, I.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 280
- Issue
- 47
- Pages
- 39582-39593
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2027442494
- Cited by
- 339
- References
- 10
- FWCI
- 7.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
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