Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Slanovc, J; Mikulčić, M; Jahn, N; Wizsy, NGT; Sattler, W; Malle, E; Hrzenjak, A.
Prostaglandin 15d-PGJ₂ inhibits proliferation of lung adenocarcinoma cells by inducing ROS production and activation of apoptosis via sirtuin-1.
Biochim Biophys Acta Mol Basis Dis. 2024; 1870(1):166924 Doi: 10.1016/j.bbadis.2023.166924
Web of Science PubMed FullText FullText_MUG

 

Leading authors Med Uni Graz

Hrzenjak Andelko

Slanovc Julia

Co-authors Med Uni Graz

Ghaffari Tabrizi-Wizsy Nassim

Malle Ernst

Mikulcic Mateja

Sattler Wolfgang

Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Abstract:

Lung adenocarcinoma (LUADC) belongs to the most prevalent and lethal cancer types. As 15-deoxy-Δ12,14-prostaglandin J₂ (15d-PGJ₂) displays anti-oxidative, -inflammatory, and -cancer properties, we investigated whether this cyclopentenone PG, a stable degradation end-product of cyclooxygenase-generated PGD₂, exerts beneficial effects in three LUADC cell lines (A549, H1299, H23). We here report that 15d-PGJ₂ had substantial cytotoxic effects in all three LUADC cell lines by promoting early apoptosis and inhibiting the cell cycle, proliferation, and migration. As indicators of cell malignancy, scratch closure and colony formation were significantly inhibited by 15d-PGJ₂. 15d-PGJ₂ induced generation of ROS and subsequent activation of MAPKs. Expression of Nrf-2, a well-known tumor driver, was markedly diminished by 15d-PGJ₂ treatment. Although PPARγ, DP1, and DP2 are expressed in LUADC cells, blocking these receptors with specific inhibitors (SR16832 and BW245C) did not reverse 15d-PGJ₂-mediated cytotoxicity, suggesting receptor-independent effects. 15d-PGJ₂ decreased SIRT1 expression in LUADC cells and the knockdown of SIRT1 diminished the cytotoxic effects of 15d-PGJ₂. Importantly, 15d-PGJ₂ significantly reduced tumor growth using the chorioallantoic membrane (CAM) assay. The structural analog of 15d- PGJ₂, 9,10-dihydro-15d-PGJ₂ (lacking the α,β-unsaturated ketone structural element), did not show any toxic effects in LUADC cells. Altogether, our findings suggest that 15d-PGJ₂ led to significantly reduced tumor growth and cell proliferation in three LUADC cell lines. The CAM assay results suggest that 15d-PGJ₂ is a suitable endogenous compound to interfere with LUADC tumor progression. We show that SIRT1 modulates the effects of 15d-PGJ₂ and may be used as a therapeutic target for LUADC.

Find related publications in this database (using NLM MeSH Indexing)

Humans - administration & dosage

Prostaglandins - pharmacology

Reactive Oxygen Species - metabolism

Sirtuin 1 - administration & dosage

Prostaglandin D2 - pharmacology

Cyclooxygenase 2 - administration & dosage

Neoplasms - administration & dosage

Adenocarcinoma of Lung - drug therapy

Apoptosis - administration & dosage

Cell Proliferation - administration & dosage

Find related publications in this database (Keywords)

Lung adenocarcinoma

Prostaglandins

Apoptosis

Reactive oxygen species

Chorioallantoic membrane assay

SIRT1

© Med Uni Graz • Imprint