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Sensitivity of Osteosarcoma Cells to Concentration-Dependent Bioactivities of Lipid Peroxidation Product 4-Hydroxynonenal Depend on Their Level of Differentiation

1
Laboratory for Oxidative Stress (LabOS), Division of Molecular Medicine, Rudjer Boskovic Institute, HR-10000 Zagreb, Croatia
2
Institute of Molecular Biosciences, Bio TechMed-Graz, University of Graz, 8010 Graz, Austria
3
University Clinic of Traumatology, University of Graz, 8010 Graz, Austria
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Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
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Department of Physiological Chemistry, Faculty of Chemistry, University of Vienna, A-1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Academic Editor: Alex Kalyuzhny
Cells 2021, 10(2), 269; https://doi.org/10.3390/cells10020269
Received: 20 December 2020 / Revised: 21 January 2021 / Accepted: 26 January 2021 / Published: 29 January 2021
4-Hydroxynonenal (HNE) is a major aldehydic product of lipid peroxidation known to exert several biological effects. Normal and malignant cells of the same origin express different sensitivity to HNE. We used human osteosarcoma cells (HOS) in different stages of differentiation in vitro, showing differences in mitosis, DNA synthesis, and alkaline phosphatase (ALP) staining. Differentiated HOS cells showed decreased proliferation (3H-thymidine incorporation), decreased viability (thiazolyl blue tetrazolium bromide-MTT), and increased apoptosis and necrosis (nuclear morphology by staining with 4′,6-diamidino-2-phenylindole-DAPI). Differentiated HOS also had less expressed c-MYC, but the same amount of c-FOS (immunocytochemistry). When exposed to HNE, differentiated HOS produced more reactive oxygen species (ROS) in comparison with undifferentiated HOS. To clarify this, we measured HNE metabolism by an HPLC method, total glutathione (GSH), oxidized GSH (ox GSH), glutathione transferase activity (GST), proteasomal activity by enzymatic methods, HNE-protein adducts by genuine ELISA and fatty acid composition by GC-MS in these cell cultures. Differentiated HOS cells had less GSH, lower HNE metabolism, increased formation of HNE-protein adducts, and lower proteasomal activity, in comparison to undifferentiated counterpart cells, while GST and oxGSH were the same. Fatty acids analyzed by GC-MS showed that there is an increase in C20:3 in differentiated HOS while the amount of C20:4 remained the same. The results showed that the cellular machinery responsible for protection against toxicity of HNE was less efficient in differentiated HOS cells. Moreover, differentiated HOS cells contained more C20:3 fatty acid, which might make them more sensitive to free radical-initiated oxidative chain reactions and more vulnerable to the effects of reactive aldehydes such as HNE. We propose that HNE might act as natural promotor of decay of malignant (osteosarcoma) cells in case of their differentiation associated with alteration of the lipid metabolism. View Full-Text
Keywords: 4-hydroxynonenal; human osteosarcoma; differentiation; proliferation; apoptosis; ALP; GSH; GST; proteasomal activity; HNE-protein adducts; fatty acid; C20:3 4-hydroxynonenal; human osteosarcoma; differentiation; proliferation; apoptosis; ALP; GSH; GST; proteasomal activity; HNE-protein adducts; fatty acid; C20:3
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MDPI and ACS Style

Sunjic, S.B.; Gasparovic, A.C.; Jaganjac, M.; Rechberger, G.; Meinitzer, A.; Grune, T.; Kohlwein, S.D.; Mihaljevic, B.; Zarkovic, N. Sensitivity of Osteosarcoma Cells to Concentration-Dependent Bioactivities of Lipid Peroxidation Product 4-Hydroxynonenal Depend on Their Level of Differentiation. Cells 2021, 10, 269. https://doi.org/10.3390/cells10020269

AMA Style

Sunjic SB, Gasparovic AC, Jaganjac M, Rechberger G, Meinitzer A, Grune T, Kohlwein SD, Mihaljevic B, Zarkovic N. Sensitivity of Osteosarcoma Cells to Concentration-Dependent Bioactivities of Lipid Peroxidation Product 4-Hydroxynonenal Depend on Their Level of Differentiation. Cells. 2021; 10(2):269. https://doi.org/10.3390/cells10020269

Chicago/Turabian Style

Sunjic, Suzana B., Ana C. Gasparovic, Morana Jaganjac, Gerald Rechberger, Andreas Meinitzer, Tilman Grune, Sepp D. Kohlwein, Branka Mihaljevic, and Neven Zarkovic. 2021. "Sensitivity of Osteosarcoma Cells to Concentration-Dependent Bioactivities of Lipid Peroxidation Product 4-Hydroxynonenal Depend on Their Level of Differentiation" Cells 10, no. 2: 269. https://doi.org/10.3390/cells10020269

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