Purchase this article with an account.
S. Theodoropoulou, P. E. Kolovou, Y. Morizane, M. Kayama, F. Nicolaou, J. W. Miller, E. Gragoudas, B. R. Ksander, D. Vavvas; Retinoblastoma Cells Are Inhibited by AICAR Partially Through Activation of AMP-Dependent Kinase. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4766.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR), an analog of AMP is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. The aim of this study is to evaluate the effects of AMPK activator AICAR on the growth of retinoblastoma cell lines (Y79, WERI and RB143).
Three different cell lines (Y79, WERI, RB143) were treated with AICAR (0.5-2 mM) for 1-5 days. Cell growth was assessed by MTT assay. Cell cycle analysis was assessed with propidium iodide staining and flow cytometry. Expression of cell cycle regulators (Cyclins, S6, Acetyl-CoA Carboxylase, p21, p27, PCNA , CDK2 and CDK4 and NF-kB p65) was assessed by RT-PCR and Western blots.
Cell treatment with AICAR inhibited cell growth, induced apoptosis and S-phase cell cycle arrest and led to activation of AMPK. These effects were abolished by treatment with dypiridamole, an inhibitor of AICAR entrance into cells. Treatment with adenosine kinase inhibitor 5-iodotubericidin to inhibit the conversion of AICAR to ZMP (the direct activator of AMPK) reversed most of the growth inhibiting effects of AICAR indicating that some of AICAR’s anti-proliferative effect are mediated through AMPK activation. In addition, AICAR treatment was associated with inhibition of mammalian target of rapamycin (mTOR) pathway, decreased phosphorylation of ribosomal protein-S6, down-regulation of cyclins A and E, and decreased expression of p21.
Our results indicate that AICAR-induced activation of AMPK inhibits retinoblastoma cell growth. This is one of the first descriptions of a non-chemotherapeutic drug with low toxicity that may be effective in treating Retinoblastoma patients.
This PDF is available to Subscribers Only