Folia Biologica
Journal of Cellular and Molecular Biology, Charles University 

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Fol. Biol. 2024, 70, 179-188

https://doi.org/10.14712/fb2024070030179

Docosahexaenoic Acid Promotes Eryptosis and Haemolysis through Oxidative Stress/Calcium/Rac1 GTPase Signalling

Feryal H. Alharthy, Jawaher Alsughayyir, Mohammad A. Alfhili

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia

Received July 2024
Accepted August 2024

References

1. Alamri, H. S., Alsughayyir, J., Akiel, M. et al. (2020) Stimulation of calcium influx and CK1α by NF-κB antagonist [6]-Gingerol reprograms red blood cell longevity. J. Food Biochem. 45, 1-9.
2. Alfhili, M. A., Alyousef, A. M., Alsughayyir, J. (2023) Tamoxifen induces eryptosis through calcium accumulation and oxidative stress. Med. Oncol. 40, 1-11. <https://doi.org/10.1007/s12032-023-02205-4>
3. Alghareeb, S., Alfhili, M., Alsughayyir, J. (2023a) Rosmarinic acid elicits calcium-dependent and sucrose-sensitive eryptosis and hemolysis through p38 MAPK, CK1α, and PKC. Molecules 28, 1-17.
4. Alghareeb, S., Alsughayyir, J., Alfhili, M. (2023b) Eriocitrin disrupts erythrocyte membrane asymmetry through oxidative stress and calcium signaling and the activation of casein kinase 1 α and Rac1 GTPase. Pharmaceuticals (Basel) 16, 1-14. <https://doi.org/10.3390/ph16121681>
5. Alghareeb, S., Alsughayyir, J., Alfhili, M. (2023c) Stimulation of hemolysis and eryptosis by α-mangostin through Rac1 GTPase and oxidative injury in human red blood cells. Molecules 28, 1-12.
6. Badheeb, A. M., Ahmed, F., Badheeb, M. A. et al. (2023) Anemia profiles in cancer patients: prevalence, contributing factors, and insights from a retrospective study at a single cancer center in Saudi Arabia. Cureus 15, e42400.
7. Brown, I., Lee, J., Sneddon, A. A. et al. (2020) Anticancer effects of n-3 EPA and DHA and their endocannabinoid derivatives on breast cancer cell growth and invasion. Prostaglandins Leukot. Essent. Fatty Acids 156, 102024. <https://doi.org/10.1016/j.plefa.2019.102024>
8. Calder, P. C. (2014) Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1851, 469-484. <https://doi.org/10.1016/j.bbalip.2014.08.010>
9. Cavazos, D. A., Price, R. S., Apte, S. S. et al. (2011) Docosahexaenoic acid selectively induces human prostate cancer cell sensitivity to oxidative stress through modulation of NF-κB. Prostate 71, 1420-1428. <https://doi.org/10.1002/pros.21359>
10. D’Eliseo, D., Velotti, F. (2016) Omega-3 fatty acids and cancer cell cytotoxicity: implications for multi-targeted cancer therapy. J. Clin. Med. 5, 15. <https://doi.org/10.3390/jcm5020015>
11. Daak, A. A., Elderdery, A. Y., Elbashir, L. M. et al. (2015) Omega 3 (n-3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease. Blood Cells Mol. Dis. 55, 48-55. <https://doi.org/10.1016/j.bcmd.2015.03.014>
12. Daak, A. A., Ghebremeskel, K., Mariniello, K. et al. (2013) Docosahexaenoic and eicosapentaenoic acid supplementation does not exacerbate oxidative stress or intravascular haemolysis in homozygous sickle cell patients. Prostaglandins Leukot. Essent. Fatty Acids 89, 305-311. <https://doi.org/10.1016/j.plefa.2013.09.006>
13. Daak, A. A., Lopez-Toledano, M. A., Heeney, M. M. (2020) Biochemical and therapeutic effects of Omega-3 fatty acids in sickle cell disease. Complement. Ther. Med. 52, 102482. <https://doi.org/10.1016/j.ctim.2020.102482>
14. Farzaneh-Far, R., Harris, W. S., Garg, S. et al. (2009) Inverse association of erythrocyte n-3 fatty acid levels with inflammatory biomarkers in patients with stable coronary artery disease: the Heart and Soul Study. Atherosclerosis 205, 538-543. <https://doi.org/10.1016/j.atherosclerosis.2008.12.013>
15. Fietkau, R., Lewitzki, V., Kuhnt, T. et al. (2013) A disease-specific enteral nutrition formula improves nutritional status and functional performance in patients with head and neck and esophageal cancer undergoing chemoradiotherapy: results of a randomized, controlled, multicenter trial. Cancer 119, 3343-3353. <https://doi.org/10.1002/cncr.28197>
16. Föller, M., Lang, F. (2020) Ion transport in eryptosis, the suicidal death of erythrocytes. Front. Cell Dev. Biol. 8, 1-9. <https://doi.org/10.3389/fcell.2020.00597>
17. Fontesa, J. D., Rahmanc, F., Laceya, S. et al. (2015) Red blood cell fatty acids and biomarkers of inflammation: a cross-sectional study in a community-based cohort. Atherosclerosis 240, 431-436. <https://doi.org/10.1016/j.atherosclerosis.2015.03.043>
18. Fu, Y. Q., Zheng, J. S., Yang, B. et al. (2015) Effect of individual omega-3 fatty acids on the risk of prostate cancer: a systematic review and dose-response meta-analysis of prospective cohort studies. J. Epidemiol. 25, 261-274. <https://doi.org/10.2188/jea.JE20140120>
19. Fukui, M., Kang, K. S., Okada, K. et al. (2013) EPA, an omega-3 fatty acid, induces apoptosis in human pancreatic cancer cells: role of ROS accumulation, caspase-8 activation, and autophagy induction. J. Cell. Biochem. 203, 192-203. <https://doi.org/10.1002/jcb.24354>
20. Gamaleldin, M., Abraham, I., Meabed, M. et al. (2023) Comparative effectiveness of adding omega-3 and Manuka honey combination to conventional therapy in preventing and treating oxidative stress in pediatric β-thalassemia major – a randomized clinical trial. Eur. Rev. Med. Pharmacol. Sci. 27, 6058-6070.
21. George, A., Pushkaran, S., Konstantinidis, D. G. et al. (2013) Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease. Blood 121, 2099-2107. <https://doi.org/10.1182/blood-2012-07-441188>
22. Giriraja, K. V., Bhatnagar, S. K., Tomlinson, L. et al. (2023) An open-label, multicenter, phase 2 study of a food enriched with docosahexaenoic acid in adults with sickle cell disease. Prostaglandins Leukot. Essent. Fatty Acids 193, 102574. <https://doi.org/10.1016/j.plefa.2023.102574>
23. Grenon, S. M., Conte, M. S., Nosova, E. et al. (2013) Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease. J. Vasc. Surg. 58, 1283-1290. <https://doi.org/10.1016/j.jvs.2013.05.024>
24. Gupta, V., Bhavanasi, S., Quadir, M. et al. (2019) Protein PEGylation for cancer therapy: bench to bedside. J. Cell Commun. Signal. 13, 319-330. <https://doi.org/10.1007/s12079-018-0492-0>
25. He, J., Lin, J., Li, J. et al. (2008) Dual effects of Ginkgo biloba leaf extract on human red blood cells. Basic Clin. Pharmacol. Toxicol. 104, 138-144. <https://doi.org/10.1111/j.1742-7843.2008.00354.x>
26. Holub, B. J. (2009) Docosahexaenoic acid (DHA) and cardiovascular disease risk factors. Prostaglandins Leukot. Essent. Fatty Acids 81, 199-204. <https://doi.org/10.1016/j.plefa.2009.05.016>
27. Hughes, D. A., Pinder, A. C., Piper, Z. et al. (1996) Fish oil supplementation inhibits the expression of major histocompatibility complex class II molecules and adhesion molecules on human monocytes. Am. J. Clin. Nutr. 63, 267-272. <https://doi.org/10.1093/ajcn/63.2.267>
28. Kalfa, T. A., Pushkaran, S., Mohandas, N. et al. (2006) Rac GTPases regulate the morphology and deformability of the erythrocyte cytoskeleton. Blood 108, 3637-3645. <https://doi.org/10.1182/blood-2006-03-005942>
29. Khan, S. U., Lone, A. N., Khan, M. S. et al. (2021) Effect of omega-3 fatty acids on cardiovascular outcomes: a systematic review and meta-analysis. EClinicalMedicine 38, 1-10. <https://doi.org/10.1016/j.eclinm.2021.100997>
30. Konstantinidis, D., George, A., Kalfa, T. A. (2010) Rac GTP­ases in erythroid biology. Transfus. Clin. Biol. 17, 126-130. <https://doi.org/10.1016/j.tracli.2010.05.002>
31. Kousparou, C., Fyrilla, M., Stephanou, A. et al. (2023) DHA/EPA (Omega-3) and LA/GLA (Omega-6) as bioactive molecules in neurodegenerative diseases. Int. J. Mol. Sci. 24, 1-21. <https://doi.org/10.3390/ijms241310717>
32. Lang, E., Lang, F. (2015) Mechanisms and pathophysiological significance of eryptosis, the suicidal erythrocyte death. Semin. Cell Dev. Biol. 39, 35-42. <https://doi.org/10.1016/j.semcdb.2015.01.009>
33. Lang, F., Lang, E., Fller, M. (2012) Physiology and pathophysiology of eryptosis. Transfus. Med. Hemother. 39, 308-314. <https://doi.org/10.1159/000342534>
34. Maćczak, A., Cyrkler, M., Bukowska, B. et al. (2015) Eryptosis-inducing activity of bisphenol A and its analogues in human red blood cells (in vitro study). J. Hazard. Mater. 307, 328-335. <https://doi.org/10.1016/j.jhazmat.2015.12.057>
35. McGlory, C., Calder, P. C., Nunes, E. A. (2019) The influence of omega-3 fatty acids on skeletal muscle protein turnover in health, disuse, and disease. Front. Nutr. 6, 1-13. <https://doi.org/10.3389/fnut.2019.00144>
36. Miles, E. A., Thies, F., Wallace, F. A. et al. (2001) Influence of age and dietary fish oil on plasma soluble adhesion molecule concentrations. Clin. Sci. 100, 91-100. <https://doi.org/10.1042/cs1000091>
37. Newell, M., Baker, K., Postovit, L. M. et al. (2017) A critical review on the effect of docosahexaenoic acid (Dha) on cancer cell cycle progression. Int. J. Mol. Sci. 18, 1-14. <https://doi.org/10.3390/ijms18081784>
38. Okpala, I., Ibegbulam, O., Duru, A. et al. (2011) Pilot study of omega-3 fatty acid supplements in sickle cell disease. APMIS 119, 442-448. <https://doi.org/10.1111/j.1600-0463.2011.02751.x>
39. Park, M., Lim, J. W., Kim, H. (2018) Docoxahexaenoic acid induces apoptosis of pancreatic cancer cells by suppressing activation of STAT3 and NF-κB. Nutrients 10, 1-14.
40. Pizato, N., Luzete, B. C., Kiffer, L. F. M. V. et al. (2018) Omega-3 docosahexaenoic acid induces pyroptosis cell death in triple-negative breast cancer cells. Sci. Rep. 8, 1-12.
41. Pretorius, E., Du Plooy, J. N., Bester, J. (2016) A comprehensive review on eryptosis. Cell. Physiol. Biochem. 39, 1977-2000. <https://doi.org/10.1159/000447895>
42. Ramiro-Cortijo, D., de Pablo, Á. L. L., López-Giménez, M. R. et al. (2020) Plasma oxidative status in preterm infants receiving LCPUFA supplementation: a pilot study. Nutrients 12, 1-15.
43. Sakuragi, T., Nagata, S. (2023) Regulation of phospholipid distribution in the lipid bilayer by flippases and scrambl­ases. Nat. Rev. Mol. Cell Biol. 24, 576-596. <https://doi.org/10.1038/s41580-023-00604-z>
44. Skouroliakou, M., Konstantinou, D., Agakidis, C. et al. (2016) Parenteral MCT/ω-3 polyunsaturated fatty acid-enriched intravenous fat emulsion is associated with cytokine and fatty acid profiles consistent with attenuated inflammatory response in preterm neonates: a randomized, double-blind clinical trial. Nutr. Clin. Pract. 31, 235-244. <https://doi.org/10.1177/0884533615602011>
45. Smith, W. L., Malkowski, M. G. (2019) Interactions of fatty acids, nonsteroidal anti-inflammatory drugs, and coxibs with the catalytic and allosteric subunits of cyclooxygenases-1 and -2. J. Biol. Chem. 294, 1697-1705. <https://doi.org/10.1074/jbc.TM118.006295>
46. So, W. W., Liu, W. N., Leung, K. N. (2015) Omega-3 polyunsaturated fatty acids trigger cell cycle arrest and induce apoptosis in human neuroblastoma LA-N-1 cells. Nutrients 7, 6956-6973. <https://doi.org/10.3390/nu7085319>
47. Spencer, L., Mann, C., Metcalfe, M. et al. (2009) The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur. J. Cancer 45, 2077-2086. <https://doi.org/10.1016/j.ejca.2009.04.026>
48. Stillwell, W., Wassall, S. R. (2003) Docosahexaenoic acid: membrane properties of a unique fatty acid. Chem. Phys. Lipids 126, 1-27. <https://doi.org/10.1016/S0009-3084(03)00101-4>
49. Sun, S. N., Jia, W. D., Chen, H. et al. (2013) Docosahexaenoic acid (DHA) induces apoptosis in human hepatocellular carcinoma cells. Int. J. Clin. Exp. Pathol. 6, 281-289.
50. Tkachenko, A., Onishchenko, A. (2023) Casein kinase 1α mediates eryptosis: a review. Apoptosis 28, 1-19. <https://doi.org/10.1007/s10495-022-01776-3>
51. Victory, R., Saed, G. M., Diamond, M. P. (2007) Antiadhesion effects of docosahexaenoic acid on normal human peritoneal and adhesion fibroblasts. Fertil. Steril. 88, 1657-1662. <https://doi.org/10.1016/j.fertnstert.2007.01.123>
52. Volpato, M., Hull, M. A. (2018) Omega-3 polyunsaturated fatty acids as adjuvant therapy of colorectal cancer. Cancer Metastasis Rev. 37, 545-555. <https://doi.org/10.1007/s10555-018-9744-y>
53. West, L., Yin, Y., Pierce, S. R. et al. (2020) Docosahexaenoic acid (DHA), an omega-3 fatty acid, inhibits tumor growth and metastatic potential of ovarian cancer. Am. J. Cancer Res. 10, 4450-4463.
54. Xue, M., Wang, Q., Zhao, J. et al. (2014) Docosahexaenoic acid inhibited the Wnt/β-catenin pathway and suppressed breast cancer cells in vitro and in vivo. J. Nutr. Biochem. 25, 104-110. <https://doi.org/10.1016/j.jnutbio.2013.09.008>
55. Yamagami, T., Porada, C. D., Pardini, R. S. et al. (2009) Docosahexaenoic acid induces dose dependent cell death in an early undifferentiated subtype of acute myeloid leukemia cell line. Cancer Biol. Ther. 8, 331-337. <https://doi.org/10.4161/cbt.8.4.7334>
56. Zelenak, C., Eberhard, M., Jilani, K. et al. (2012) Protein kinase CK1 α regulates erythrocyte survival. Cell. Physiol. Biochem. 13, 171-180. <https://doi.org/10.1159/000337598>
57. Zhbanov, A., Yang, S. (2015) Effects of aggregation on blood sedimentation and conductivity. PLoS One 10, 1-25. <https://doi.org/10.1371/journal.pone.0129337>
58. Zimmer, S., Goody, P. R., Oelze, M. et al. (2021) Inhibition of Rac1 GTPase decreases vascular oxidative stress, improves endothelial function, and attenuates atherosclerosis development in mice. Front. Cardiovasc. Med. 8, 1-11. <https://doi.org/10.3389/fcvm.2021.680775>
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