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

作者：Parenti S; Casagrande G; Montanari M; Espahbodinia M; Ettari R; Grande A; Corsi L^*

来源：Life Sciences, 2016, 152: 117-125.

DOI：10.1016/j.lfs.2016.03.051

• Cell cycle
• G(2)/M check point
• Myt-1
• Apoptosis
• Growth inhibition
• 2,3-Benzodiazepine-3-one

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-4one 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 G(2)/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. Although 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 G(2)/M checkpoint regulation pathway.
Finally, our data suggest that compound 1 g might be a good molecule for future development in the cancer research.

• 出版日期2016-5-1