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Plos One : Aminoimidazole Carboxamide Ribonucleotide Aicar Inhibits the Growth of Retinoblastoma in Vivo by Decreasing Angiogenesis and Inducing Apoptosis, Volume 8

By Srivastava, Rakesh K.

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Book Id: WPLBN0003943666
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Reproduction Date: 2015

Title: Plos One : Aminoimidazole Carboxamide Ribonucleotide Aicar Inhibits the Growth of Retinoblastoma in Vivo by Decreasing Angiogenesis and Inducing Apoptosis, Volume 8  
Author: Srivastava, Rakesh K.
Volume: Volume 8
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Historic
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Publisher: Plos

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Srivastava, R. K. (n.d.). Plos One : Aminoimidazole Carboxamide Ribonucleotide Aicar Inhibits the Growth of Retinoblastoma in Vivo by Decreasing Angiogenesis and Inducing Apoptosis, Volume 8. Retrieved from http://www.ebooklibrary.org/


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Description : 5-Aminoimidazole-4-carboxamide-1-b-4-ribofuranoside (AICAR), an analog of AMP is widely used as an activator of AMPkinase (AMPK), a protein that regulates the responses of the cell to energy change. Recently, we showed that AICAR-induced AMPK activation inhibits the growth of retinoblastoma cells in vitro by decreasing cyclins and by inducing apoptosis and Sphase arrest. In this study, we investigated the effects of AMPK activator AICAR on the growth of retinoblastoma in vivo. Intraperitoneal injection of AICAR resulted in 48% growth inhibition of Y79 retinoblastoma cell tumors in mice. Tumors isolated from mice treated with AICAR had decreased expression of Ki67 and increased apoptotic cells (TUNEL positive) compared with the control. In addition, AICAR treatment suppressed significantly tumor vessel density and macrophage infiltration. We also showed that AICAR administration resulted in AMPK activation and mTOR pathway inhibition. Paradoxically observed down-regulation of p21, which indicates that p21 may have a novel function of an oncogene in retinoblastoma tumor. Our results indicate that AICAR treatment inhibited the growth of retinoblastoma tumor in vivo via AMPK/mTORC1 pathway and by apoptogenic, anti-proliferative, anti-angiogenesis mechanism. AICAR is a promising novel non-chemotherapeutic drug that may be effective as an adjuvant in treating Retinoblastoma.

 

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