Glyoxalase I inhibition induces apoptosis in irradiated MCF-7 cells via a novel mechanism involving Hsp27, p53 and NF-κB

Abstract

Background:Glyoxalase I (GI) is a cellular defence enzyme involved in the detoxification of methylglyoxal (MG), a cytotoxic byproduct of glycolysis, and MG-derived advanced glycation end products (AGEs). Argpyrimidine (AP), one of the major AGEs coming from MG modifications of proteins arginines, is a pro-apoptotic agent. Radiotherapy is an important modality widely used in cancer treatment. Exposure of cells to ionising radiation (IR) results in a number of complex biological responses, including apoptosis. The present study was aimed at investigating whether, and through which mechanism, GI was involved in IR-induced apoptosis.Methods:Apoptosis, by TUNEL assay, transcript and protein levels or enzymatic activity, by RT–PCR, western blot and spectrophotometric methods, respectively, were evaluated in irradiated MCF-7 breast cancer cells, also in experiments with appropriate inhibitors or using small interfering RNA.Results:Ionising radiation induced a dramatic reactive oxygen species (ROS)-mediated inhibition of GI, leading to AP-modified Hsp27 protein accumulation that, in a mechanism involving p53 and NF-κB, triggered an apoptotic mitochondrial pathway. Inhibition of GI occurred at both functional and transcriptional levels, the latter occurring via ERK1/2 MAPK and ERα modulation.Conclusions:Glyoxalase I is involved in the IR-induced MCF-7 cell mitochondrial apoptotic pathway via a novel mechanism involving Hsp27, p53 and NF-κB.

DOI: 10.1038/bjc.2014.280

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@inproceedings{Antognelli2014GlyoxalaseII, title={Glyoxalase I inhibition induces apoptosis in irradiated MCF-7 cells via a novel mechanism involving Hsp27, p53 and NF-κB}, author={Cinzia Antognelli and Isabella M Palumbo and Cynthia Aristei and Vincenzo Nicola Talesa}, booktitle={British Journal of Cancer}, year={2014} }