Glucose Increases Proliferation and Chemoresistance in Chronic Myeloid Leukemia Via Decreasing Antioxidant Properties of ω-3 Polyunsaturated Fatty Acids in the Presence of Iron

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2023 Nov 16

PMID 37971569

Authors

Samira Shahraki

Fatemeh Bahraini

Behzad Mesbahzadeh

Mahtab Sayadi

Seyed Mehdi Sajjadi

Affiliations

Soon will be listed here.

Abstract

Background: There is a strong association between hyperglycemia, oxidative stress, inflammation and the onset and progression of diabetes which causes a higher risk of cancer. This study investigated, the effect of concomitant use of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) with iron supplements in hyper-glucose conditions on the K-562 cell line.

Methods: The effects of iron, ω-3 PUFAs, and a combination of both on K-562 cells were investigated under normal and high glucose conditions. The impact of these treatments was evaluated using multiple methodologies, including the MTT assay for cell viability, quantification of oxidative stress markers [total antioxidant capacity (TAC) and malondialdehyde (MDA)], and analysis of the cell cycle. Furthermore, the expression levels of TNFα and p53 mRNA were measured using Real-time PCR.

Results: The co-treatment of ω-3 PUFAs and iron in the presence of high glucose had notable effects, as evidenced by an increase in cell survival, resistance to imatinib chemotherapy, TNFαmRNA expression levels, MDA levels, and percentage of cells in the G2/S phase. Additionally, there was a decrease in the mRNA expression of p53 and TAC levels compared to treatment in the normal-glucose condition.

Conclusion: Hyperglycemic conditions in conjunction with the combined treatment of theω-3 PUFAs and iron, led to reduced anticancer capacity, chemosensitivity, anti-inflammatory and antioxidant properties of the K-562 cells. These effects were found to be mediated by oxidative stress.

References

Mayer-Davis E, Lawrence J, Dabelea D, Divers J, Isom S, Dolan L . Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002-2012. N Engl J Med. 2017; 376(15):1419-1429. PMC: 5592722. DOI: 10.1056/NEJMoa1610187. View

Yaribeygi H, Atkin S, Sahebkar A . A review of the molecular mechanisms of hyperglycemia-induced free radical generation leading to oxidative stress. J Cell Physiol. 2018; 234(2):1300-1312. DOI: 10.1002/jcp.27164. View

Qi L, Qi X, Xiong H, Liu Q, Li J, Zhang Y . Type 2 diabetes mellitus and risk of malignant melanoma: a systematic review and meta-analysis of cohort studies. Iran J Public Health. 2015; 43(7):857-66. PMC: 4401051. View

Nimmanapalli R, Bhalla K . Mechanisms of resistance to imatinib mesylate in Bcr-Abl-positive leukemias. Curr Opin Oncol. 2002; 14(6):616-20. DOI: 10.1097/00001622-200211000-00005. View

Kim J, Chu S, Gramlich J, Pride Y, Babendreier E, Chauhan D . Activation of the PI3K/mTOR pathway by BCR-ABL contributes to increased production of reactive oxygen species. Blood. 2004; 105(4):1717-23. DOI: 10.1182/blood-2004-03-0849. View

Glowacki S, Synowiec E, Blasiak J . The role of mitochondrial DNA damage and repair in the resistance of BCR/ABL-expressing cells to tyrosine kinase inhibitors. Int J Mol Sci. 2013; 14(8):16348-64. PMC: 3759915. DOI: 10.3390/ijms140816348. View

Cohen P, Cross D, Janne P . Kinase drug discovery 20 years after imatinib: progress and future directions. Nat Rev Drug Discov. 2021; 20(7):551-569. PMC: 8127496. DOI: 10.1038/s41573-021-00195-4. View

Amarante-Mendes G, Rana A, Datoguia T, Hamerschlak N, Brumatti G . BCR-ABL1 Tyrosine Kinase Complex Signaling Transduction: Challenges to Overcome Resistance in Chronic Myeloid Leukemia. Pharmaceutics. 2022; 14(1). PMC: 8780254. DOI: 10.3390/pharmaceutics14010215. View

Glowacki S, Synowiec E, Szwed M, Toma M, Skorski T, Sliwinski T . Relationship between Oxidative Stress and Imatinib Resistance in Model Chronic Myeloid Leukemia Cells. Biomolecules. 2021; 11(4). PMC: 8074285. DOI: 10.3390/biom11040610. View

10.

de Bus I, Witkamp R, Zuilhof H, Albada B, Balvers M . The role of n-3 PUFA-derived fatty acid derivatives and their oxygenated metabolites in the modulation of inflammation. Prostaglandins Other Lipid Mediat. 2019; 144:106351. DOI: 10.1016/j.prostaglandins.2019.106351. View

11.

Moloudizargari M, Mortaz E, Asghari M, Adcock I, Redegeld F, Garssen J . Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review. Oncotarget. 2018; 9(14):11858-11875. PMC: 5837752. DOI: 10.18632/oncotarget.24405. View

12.

Kheyrandish S, Rastgar A, Hamidi M, Sajjadi S, Sarab G . Evaluation of anti-tumor effect of the exopolysaccharide from new cold-adapted yeast, Rhodotorula mucilaginosa sp. GUMS16 on chronic myeloid leukemia K562 cell line. Int J Biol Macromol. 2022; 206:21-28. DOI: 10.1016/j.ijbiomac.2022.02.113. View

13.

Rastgar A, Sayadi M, Anani-Sarab G, Sajjadi S . Astaxanthin decreases the growth-inhibitory dose of cytarabine and inflammatory response in the acute lymphoblastic leukemia cell line NALM-6. Mol Biol Rep. 2022; 49(7):6415-6422. DOI: 10.1007/s11033-022-07452-8. View

14.

Lawrence G . Perspective: The Saturated Fat-Unsaturated Oil Dilemma: Relations of Dietary Fatty Acids and Serum Cholesterol, Atherosclerosis, Inflammation, Cancer, and All-Cause Mortality. Adv Nutr. 2021; 12(3):647-656. PMC: 8166560. DOI: 10.1093/advances/nmab013. View

15.

Dixon S, Stockwell B . The role of iron and reactive oxygen species in cell death. Nat Chem Biol. 2013; 10(1):9-17. DOI: 10.1038/nchembio.1416. View

16.

Fischbacher A, von Sonntag C, Schmidt T . Hydroxyl radical yields in the Fenton process under various pH, ligand concentrations and hydrogen peroxide/Fe(II) ratios. Chemosphere. 2017; 182:738-744. DOI: 10.1016/j.chemosphere.2017.05.039. View

17.

Ludin A, Gur-Cohen S, Golan K, Kaufmann K, Itkin T, Medaglia C . Reactive oxygen species regulate hematopoietic stem cell self-renewal, migration and development, as well as their bone marrow microenvironment. Antioxid Redox Signal. 2014; 21(11):1605-19. PMC: 4175025. DOI: 10.1089/ars.2014.5941. View

18.

Manz D, Blanchette N, Paul B, Torti F, Torti S . Iron and cancer: recent insights. Ann N Y Acad Sci. 2016; 1368(1):149-61. PMC: 4870095. DOI: 10.1111/nyas.13008. View

19.

Rochette L, Dogon G, Rigal E, Zeller M, Cottin Y, Vergely C . Lipid Peroxidation and Iron Metabolism: Two Corner Stones in the Homeostasis Control of Ferroptosis. Int J Mol Sci. 2023; 24(1). PMC: 9820499. DOI: 10.3390/ijms24010449. View

20.

Biernacka K, Uzoh C, Zeng L, Persad R, Bahl A, Gillatt D . Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2. Endocr Relat Cancer. 2013; 20(5):741-51. DOI: 10.1530/ERC-13-0077. View