Myeloperoxidase Alters Lung Cancer Cell Function to Benefit Their Survival
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Myeloperoxidase Alters Lung Cancer Cell Function to Benefit Their Survival. / 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.
I: Antioxidants, Bind 12, Nr. 8, 1587, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Myeloperoxidase Alters Lung Cancer Cell Function to Benefit Their Survival
AU - Cosic-Mujkanovic, Nejra
AU - Valadez-Cosmes, Paulina
AU - Maitz, Kathrin
AU - Lueger, Anna
AU - Mihalic, Zala N.
AU - Runtsch, Marah C.
AU - Kienzl, Melanie
AU - Davies, Michael J.
AU - Chuang, Christine Y.
AU - Heinemann, Akos
AU - Schicho, Rudolf
AU - Marsche, Gunther
AU - Kargl, Julia
N1 - Publisher Copyright: © 2023 by the authors.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - A549 cells
KW - apoptosis
KW - myeloperoxidase (MPO)
KW - neutrophil
KW - non-small-cell lung cancer (NSCLC)
KW - proliferation
UR - http://www.scopus.com/inward/record.url?scp=85169123429&partnerID=8YFLogxK
U2 - 10.3390/antiox12081587
DO - 10.3390/antiox12081587
M3 - Journal article
C2 - 37627581
AN - SCOPUS:85169123429
VL - 12
JO - Antioxidants
JF - Antioxidants
SN - 2076-3921
IS - 8
M1 - 1587
ER -
ID: 369870329