It has been shown that the antagonism of glutamate receptors activity was able inhibit proliferation and induce apoptosis in several neuronal and non-neuronal cancer cell lines. In addition, it has been shown that glutamate might facilitate the spread and growth of leukemia T cells through interactions with AMPA receptors. The aim of the present study was to investigate the modulation of cell cycle elicited by a novel 2,3-benzodiazepine-4- one non-competitive AMPA antagonist derivative in the human leukemia Jurkat T cells. Our results indicated that the 1-(4-amino-3,5-dimethylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4 h-2,3- benzodiazepin-4-one, named 1 g, exerted a significant growth inhibition of leukemia Jurkat T cells in a time and dose dependent manner, arresting the transition of G2/M phase through activation of Myt-1. The molecule also induced apoptosis through the enhanced expression of the pro-apoptotic p53, and the inhibition of Bcl-2, and Bcl-xl, followed by the activation of caspase-3. The results suggested that compound 1 g might act mostly as a cytostatic rather than cytotoxic compound. Al- though further studies are necessary, in order to identify others specific pathways involved in the activity of the present molecule, the presented results identified a novel molecule acting on specific G2/M checkpoint reg- ulation pathway. Finally, our data suggest that compound 1 g might be a good molecule for future development in the cancer research

A novel 2,3-benzodiazepine-4-one derivative AMPA antagonist inhibits G2/M transition and induces apoptosis in human leukemia Jurkat T cell line / Parenti, Sandra; Casagrande, Giacomo; Montanari, Monica; Espahbodinia, M.; Ettari, R.; Grande, Alexis; Corsi, Lorenzo. - In: LIFE SCIENCES. - ISSN 0024-3205. - ELETTRONICO. - 152:(2016), pp. 117-125. [10.1016/j.lfs.2016.03.051]

A novel 2,3-benzodiazepine-4-one derivative AMPA antagonist inhibits G2/M transition and induces apoptosis in human leukemia Jurkat T cell line

PARENTI, Sandra;CASAGRANDE, GIACOMO;MONTANARI, Monica;GRANDE, Alexis;CORSI, Lorenzo
2016

Abstract

It has been shown that the antagonism of glutamate receptors activity was able inhibit proliferation and induce apoptosis in several neuronal and non-neuronal cancer cell lines. In addition, it has been shown that glutamate might facilitate the spread and growth of leukemia T cells through interactions with AMPA receptors. The aim of the present study was to investigate the modulation of cell cycle elicited by a novel 2,3-benzodiazepine-4- one non-competitive AMPA antagonist derivative in the human leukemia Jurkat T cells. Our results indicated that the 1-(4-amino-3,5-dimethylphenyl)-3,5-dihydro-7,8-ethylenedioxy-4 h-2,3- benzodiazepin-4-one, named 1 g, exerted a significant growth inhibition of leukemia Jurkat T cells in a time and dose dependent manner, arresting the transition of G2/M phase through activation of Myt-1. The molecule also induced apoptosis through the enhanced expression of the pro-apoptotic p53, and the inhibition of Bcl-2, and Bcl-xl, followed by the activation of caspase-3. The results suggested that compound 1 g might act mostly as a cytostatic rather than cytotoxic compound. Al- though further studies are necessary, in order to identify others specific pathways involved in the activity of the present molecule, the presented results identified a novel molecule acting on specific G2/M checkpoint reg- ulation pathway. Finally, our data suggest that compound 1 g might be a good molecule for future development in the cancer research
6-apr-2016
152
117
125
A novel 2,3-benzodiazepine-4-one derivative AMPA antagonist inhibits G2/M transition and induces apoptosis in human leukemia Jurkat T cell line / Parenti, Sandra; Casagrande, Giacomo; Montanari, Monica; Espahbodinia, M.; Ettari, R.; Grande, Alexis; Corsi, Lorenzo. - In: LIFE SCIENCES. - ISSN 0024-3205. - ELETTRONICO. - 152:(2016), pp. 117-125. [10.1016/j.lfs.2016.03.051]
Parenti, Sandra; Casagrande, Giacomo; Montanari, Monica; Espahbodinia, M.; Ettari, R.; Grande, Alexis; Corsi, Lorenzo
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1100681
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