Relationships between level of lipid peroxidation products and expression of Nrf2 and its activators/ inhibitors in non-small cell lung cancer tissue.

Abstract

Lung cancer development is characterized by oxidative stress that leads to the oxidative modifications of cellular components, including phospholipid and protein. Lipid peroxidation products may be involved in intracellular signaling pathways or in the activity of transcription factors (Nrf2). Therefore, the aim of this study has been to evaluate the relationship between the level of reactive aldehydes and the activity of the transcription factor and a comparison of these parameters in different histological types and stages of non-small cell lung cancer. Lung cancer tissues and tissues without morphological changes were received during operation from patients with squamous cell lung carcinoma (SqCC), lung adenocarcinoma (AC) and large cell lung carcinoma (LCC). In the tissue homogenates the level of reactive aldehydes [4-HNE, MDA, 4-ONE] was determined by GCMS, while Nrf2 and its activators/inhibitors were evaluated by Western immunobloting. Tumor tissues showed several times higher reactive aldehydes level and those changes were accompanied by overexpression of Nrf2. The highest increase of 4-HNE and MDA level was observed in the SqCC and it was correlated with the highest increase in Nrf2 expression. Moreover, the aldehydes level and Nrf2 phosphorylation were significantly higher in the stage I than in the stage II. The level of Nrf2 inhibitor - Bach1 was lower in all histological types of tumor, but in AC was the most reduced, what is correlated with the lowest level of reactive aldehydes. The highest expression of p62 and p21 - Nrf2 activators was observed also in adenocarcinoma of the lung. However, the level of another Nrf2 activator - KAP1 was decreased in all histological types of tumor. Additionally, the cJun amount in the tumor tissue was increased, whereas reduction of its phosphorylated form in AC and LCC was observed. Understanding the relation between reactive aldehydes level and the Nrf2 activity may be applied in anticancer therapies.

• Authors: Agnieszka Gegotek, Jacek Niklinski, Radoslaw Charkiewicz, Katarzyna Bielawska, Miroslaw Kozlowski, Elzbieta Skrzydlewska
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 75 Suppl 1 Pg. S31 (Oct 2014) ISSN: 1873-4596 [Electronic] United States
• PMID: 26461337 (Publication Type: Journal Article)
• Copyright: Copyright © 2014. Published by Elsevier Inc.