title: Lipid mediators involved in the oxidative stress and antioxidant defence of human lung cancer cells.
abstract: The oxidative modifications of bioactive macromolecules have important roles in carcinogenesis. Of particular interest are lipid peroxidation products, which are involved in the activation of Nrf2 and endocannabinoids that affect cancer progression.
  
  
  
  In lung cancer tissues (squamous cell lung carcinoma - SCC and adenocarcinoma - AC), the glutathione peroxidase and catalase activity and glutathione level, together with the expression of Nrf2 and its activators/inhibitors were estimated. The oxidative modifications of DNA (8-hydroxy-2'-deoxyguanosine and N7-methylguanine), endocannabinoids (anandamide and 2- arachidonylglyceriol), their receptors (CB1/2, TRV1, GPR55), phospholipid fatty acids (arachidonic, linoleic and docosahexaenoic), and reactive aldehydes (4-hydroxynonenal, 4-oxononenal and malondialdehyde) were determined.
  
  
  
  Tumour tissues showed lower antioxidant capacity than healthy tissues, which was accompanied by lower levels of fatty acids and higher levels of reactive aldehydes. Disturbances in antioxidant capacity and enhanced DNA oxidative modifications were observed in 88% of AC patients and 81% of SCC patients. The 4-hydroxynonenal-Histidine adducts were detected in the necrotic and stromal cells in all tumours. These findings were associated with the enhanced Nrf2 activity, especially in AC. The strong difference between the cancer subtypes was evident in the levels of endocannabinoids, with an increase in 89% of SCC and a decrease in 85% of AC patients being observed. Additionally, the increase in the expression of CB1/2 receptors was observed only in 82% of AC, while the expression of VR1 and GPR55 was enhanced in 79% of SCC and 82% of AC patients.
  
  
  
  This study shows significant differences in the redox status, Nrf2 pathway and endocannabinoid system between SCC and AC tissues. Understanding the relation between the various lipid mediators and antioxidants in different lung cancer subtypes may be beginning for further research on the effective anticancer therapy.
authors: Departments of Analytical Chemistry, Medical University of Białystok, Białystok, Poland.
authors: Agnieszka
authors: A
authors: Gęgotek
authors: Clinical Molecular Biology, Medical University of Białystok, Białystok, Poland.
authors: Jacek
authors: J
authors: Nikliński
authors: LabOS, Rudjer Boskovic Institute, Zagreb, Croatia.
authors: Neven
authors: N
authors: Žarković
authors: University of Zagreb School of Medicine, Clinical Hospital Centre Division of Pathology, Zagreb, Croatia.
authors: Kamelija
authors: K
authors: Žarković
authors: Institute of Molecular Biosciences, Karl Franzens University in Graz, Austria.
authors: Georg
authors: G
authors: Waeg
authors: Departments of Analytical Chemistry, Medical University of Białystok, Białystok, Poland.
authors: Wojciech
authors: W
authors: Łuczaj
authors: Clinical Molecular Biology, Medical University of Białystok, Białystok, Poland.
authors: Radosław
authors: R
authors: Charkiewicz
authors: Departments of Analytical Chemistry, Medical University of Białystok, Białystok, Poland. Electronic address: elzbieta.skrzydlewska@umb.edu.pl.
authors: Elżbieta
authors: E
authors: Skrzydlewska
mesh_terms: D000368:Aged; D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage; D063388:Endocannabinoids / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D063388:Endocannabinoids; D051267:NF-E2-Related Factor 2; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase
keywords: Endocannabinoid system; Lung adenocarcinoma; Lung squamous cell carcinoma; Nrf2; Reactive aldehydes