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DOI: 10.1055/a-1640-8561
Selective Toxicity Effect of Fatty Acids Omega-3, 6 and 9 Combination on Glioblastoma Neurons through their Mitochondria
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Abstract
Glioblastoma (GBM) is one of the most common malignant tumors of the central nervous system that occurs in the brain and is a deadly disease. Despite the different approaches to the treatment of this malignancy, the discovery of new compounds with anti-cancer effects seems necessary. In this study, the selective toxicity effects of omega 3, 6 and 9 combinations on mitochondria isolated from U87MG human glioma cells and also human embryonic kidney 293 cells (HEK293) as normal control were investigated. The results indicated that the omega 3, 6 and 9 combinations significantly reduced succinate dehydrogenase (SDH) activity only in mitochondria isolated from U87MG human glioma cells. Additionally, exposure of mitochondria isolated from U87MG human glioma cells to this combination was associated with a selective increase in the level of reactive oxygen species (ROS), the collapse of the mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release. However, these effects were not observed in mitochondria isolated from HEK293 cells (as a normal group). According to results, it is proposed that the combination of omega 3, 6 and 9 could induce toxicity in U87MG human glioma cells through their mitochondria. This combination can be helpful as a complementary therapy in patients with GBM.
Publikationsverlauf
Eingereicht: 09. August 2021
Angenommen: 06. September 2021
Artikel online veröffentlicht:
19. Oktober 2021
© 2021. Thieme. All rights reserved.
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Germany
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References
- 1 Costa PM, Mei K-C, Kreuzer M. et al. Selective toxicity of functionalised graphene oxide to patients-derived glioblastoma stem cells and minimal toxicity to non-cancerous brain tissue cells. 2D Materials 2020; 7: 045002
- 2 Marconi GD, Gallorini M, Carradori S. et al. The Up-Regulation of Oxidative Stress as a Potential Mechanism of Novel MAO-B Inhibitors for Glioblastoma Treatment. Molecules 2019; 24
- 3 Sinaei N, Mirakabadi AZ, Behnam B. et al. Potential anticancer activity of Caspian cobra venom through induction of oxidative stress in glioblastoma cell line. Proceedings of the National Academy of Sciences, India Section B: Biological Sciences 2019; 89: 1161-1166
- 4 Ertilav K, Nazıroğlu M, Ataizi ZS. et al. Selenium Enhances the Apoptotic Efficacy of Docetaxel Through Activation of TRPM2 Channel in DBTRG Glioblastoma Cells. Neurotox Res 2019; 35: 797-808
- 5 Godoy P, Pour Khavari A, Rizzo M. et al. Targeting NRF2, Regulator of Antioxidant System, to Sensitize Glioblastoma Neurosphere Cells to Radiation-Induced Oxidative Stress. Oxid Med Cell Longev 2020; 2020: 2534643
- 6 Su BC, Pan CY, Chen JY. Antimicrobial Peptide TP4 Induces ROS-Mediated Necrosis by Triggering Mitochondrial Dysfunction in Wild-Type and Mutant p53 Glioblastoma Cells. Cancers (Basel) 2019; 11: 171
- 7 Seydi E, Rasekh HR, Salimi A. et al. Selective toxicity of apigenin on cancerous hepatocytes by directly targeting their mitochondria. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents 2016; 16: 1576-1586
- 8 Seydi E, Salimi A, Rasekh HR. et al. Selective cytotoxicity of luteolin and kaempferol on cancerous hepatocytes obtained from rat model of hepatocellular carcinoma: involvement of ROS-mediated mitochondrial targeting. Nutrition and Cancer 2018; 70: 594-604
- 9 Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacognosy Reviews 2014; 8: 122
- 10 Eckert GP, Lipka U, Muller WE. Omega-3 fatty acids in neurodegenerative diseases: focus on mitochondria. Prostaglandins Leukot Essent Fatty Acids 2013; 88: 105-114
- 11 Jaworski S, Strojny B, Sawosz E. et al. Degradation of Mitochondria and Oxidative Stress as the Main Mechanism of Toxicity of Pristine Graphene on U87 Glioblastoma Cells and Tumors and HS-5 Cells. Int J Mol Sci 2019; 20: 650
- 12 Zhang Y, Jiang L, Hu W. et al. Mitochondrial dysfunction during in vitro hepatocyte steatosis is reversed by omega-3 fatty acid-induced up-regulation of mitofusin 2. Metabolism 2011; 60: 767-775
- 13 Grasso D, Zampieri LX, Capelôa T. et al. Mitochondria in cancer. Cell Stress 2020; 4: 114
- 14 Jeena M, Kim S, Jin S. et al. Recent progress in mitochondria-targeted drug and drug-free agents for cancer therapy. Cancers 2020; 12: 4
- 15 Öztürk Y, Günaydın C, Yalçın F. et al. Resveratrol Enhances Apoptotic and Oxidant Effects of Paclitaxel through TRPM2 Channel Activation in DBTRG Glioblastoma Cells. Oxid Med Cell Longev 2019; 2019: 4619865
- 16 Modica-Napolitano JS, Singh KK. Mitochondrial dysfunction in cancer. Mitochondrion 2004; 4: 755-762
- 17 Toogood PL. Mitochondrial drugs. Current opinion in chemical biology 2008; 12: 457-463
- 18 Xiao AY, Maynard MR, Piett CG. et al. Sodium sulfide selectively induces oxidative stress, DNA damage, and mitochondrial dysfunction and radiosensitizes glioblastoma (GBM) cells. Redox Biol 2019; 26: 101220
- 19 Lei K, Xia Y, Wang XC. et al. C/EBPβ mediates NQO1 and GSTP1 anti-oxidative reductases expression in glioblastoma, promoting brain tumor proliferation. Redox Biol 2020; 34: 101578
- 20 de Oliveira MR, Nabavi SF, Nabavi SM. et al. Omega-3 polyunsaturated fatty acids and mitochondria, back to the future. Trends in Food Science & Technology 2017; 67: 76-92
- 21 Park YH, Shin SJ, Kim HS. et al. Omega-3 Fatty Acid-Type Docosahexaenoic Acid Protects against Aβ-Mediated Mitochondrial Deficits and Pathomechanisms in Alzheimer's Disease-Related Animal Model. Int J Mol Sci 2020; 21: 3879
- 22 Rovito D, Giordano C, Plastina P. et al. Omega-3 DHA- and EPA-dopamine conjugates induce PPARγ-dependent breast cancer cell death through autophagy and apoptosis. Biochim Biophys Acta 2015; 1850: 2185-2195
- 23 Sun H, Hu Y, Gu Z. et al. Omega-3 fatty acids induce apoptosis in human breast cancer cells and mouse mammary tissue through syndecan-1 inhibition of the MEK-Erk pathway. Carcinogenesis 2011; 32: 1518-1524
- 24 Zhao Y, Ye L, Liu H. et al. Vanadium compounds induced mitochondria permeability transition pore (PTP) opening related to oxidative stress. J Inorg Biochem 2010; 104: 371-378
- 25 Baracca A, Sgarbi G, Solaini G. et al. Rhodamine 123 as a probe of mitochondrial membrane potential: evaluation of proton flux through F(0) during ATP synthesis. Biochim Biophys Acta 2003; 1606: 137-146
- 26 Faizi M, Seydi E, Abarghuyi S. et al. A search for mitochondrial damage in Alzheimer’s disease using isolated rat brain mitochondria. Iranian Journal of Pharmaceutical Research 2016; 15: 185-195
- 27 Daniels TE, Olsen EM, Tyrka AR. Stress and Psychiatric Disorders: The Role of Mitochondria. Annu Rev Clin Psychol 2020; 16: 165-186
- 28 Missiroli S, Genovese I, Perrone M. et al. The Role of Mitochondria in Inflammation: From Cancer to Neurodegenerative Disorders. J Clin Med 2020; 9: 740
- 29 Kopecka J, Gazzano E, Castella B. et al. Mitochondrial metabolism: Inducer or therapeutic target in tumor immune-resistance?. Semin Cell Dev Biol 2020; 98: 80-89
- 30 Roth KG, Mambetsariev I, Kulkarni P. et al. The Mitochondrion as an Emerging Therapeutic Target in Cancer. Trends Mol Med 2020; 26: 119-134
- 31 Pourahmad J, Salimi A, Seydi E. Mitochondrial targeting for drug development. Toxicology Studies-Cells, Drugs and Environment InTech 2015; 61-82
- 32 Sakai C, Tomitsuka E, Miyagishi M. et al. Type II Fp of human mitochondrial respiratory complex II and its role in adaptation to hypoxia and nutrition-deprived conditions. Mitochondrion 2013; 13: 602-609
- 33 Chobot V, Hadacek F. Exploration of pro-oxidant and antioxidant activities of the flavonoid myricetin. Redox Rep 2011; 16: 242-247
- 34 Procházková D, Boušová I, Wilhelmová N. Antioxidant and prooxidant properties of flavonoids. Fitoterapia 2011; 82: 513-523
- 35 Shin S, Jing K, Jeong S. et al. The omega-3 polyunsaturated fatty acid DHA induces simultaneous apoptosis and autophagy via mitochondrial ROS-mediated Akt-mTOR signaling in prostate cancer cells expressing mutant p53. Biomed Res Int 2013; 2013: 568671
- 36 Bu Q, Huang Y, Li M. et al. Acrylamide exposure represses neuronal differentiation, induces cell apoptosis and promotes tau hyperphosphorylation in hESC-derived 3D cerebral organoids. Food and Chemical Toxicology 2020; 144: 111643