Cosic-Mujkanovic Nejra, Valadez-Cosmes Paulina, Maitz Kathrin, Lueger Anna, Mihalic Zala N, Runtsch Marah C, Kienzl Melanie, Davies Michael J, Chuang Christine Y, Heinemann Akos, Schicho Rudolf, Marsche Gunther, Kargl Julia
Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria.
BioTechMed-Graz, 8010 Graz, Austria.
Antioxidants (Basel). 2023 Aug 9;12(8):1587. doi: 10.3390/antiox12081587.
Myeloperoxidase (MPO) is a neutrophil-derived enzyme that has been recently associated with tumour development. However, the mechanisms by which this enzyme exerts its functions remain unclear. In this study, we investigated whether myeloperoxidase can alter the function of A549 human lung cancer cells. We observed that MPO promoted the proliferation of cancer cells and inhibited their apoptosis. Additionally, it increased the phosphorylation of AKT and ERK. MPO was rapidly bound to and internalized by A549 cells, retaining its enzymatic activity. Furthermore, MPO partially translocated into the nucleus and was detected in the chromatin-enriched fraction. Effects of MPO on cancer cell function could be reduced when MPO uptake was blocked with heparin or upon inhibition of the enzymatic activity with the MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH). Lastly, we have shown that tumour-bearing mice treated with 4-ABAH had reduced tumour burden when compared to control mice. Our results highlight the role of MPO as a neutrophil-derived enzyme that can alter the function of lung cancer cells.
髓过氧化物酶（MPO）是一种源自中性粒细胞的酶，最近被发现与肿瘤发展有关。然而，这种酶发挥其功能的机制仍不清楚。在本研究中，我们调查了髓过氧化物酶是否能改变A549人肺癌细胞的功能。我们观察到MPO促进癌细胞增殖并抑制其凋亡。此外，它增加了AKT和ERK的磷酸化。MPO迅速与A549细胞结合并被内化，同时保留其酶活性。此外，MPO部分转移到细胞核中，并在富含染色质的部分中被检测到。当用肝素阻断MPO摄取或用MPO抑制剂4-氨基苯甲酸酰肼（4-ABAH）抑制酶活性时，MPO对癌细胞功能的影响会降低。最后，我们表明，与对照小鼠相比，用4-ABAH治疗的荷瘤小鼠的肿瘤负担减轻。我们的结果突出了MPO作为一种源自中性粒细胞的酶在改变肺癌细胞功能方面的作用。
