Glucose increases proliferation and chemoresistance in chronic myeloid leukemia via decreasing antioxidant Properties of ω-3 polyunsaturated fatty acids in the presence of Iron

• Published in: Molecular biology reports 2023-12, Vol.50 (12), p.10315-10324
• Main Authors: Shahraki, Samira, Bahraini, Fatemeh, Mesbahzadeh, Behzad, Sayadi, Mahtab, Sajjadi, Seyed Mehdi
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Antioxidants; Antioxidants - pharmacology; Biomedical and Life Sciences; Cell cycle; Cell Proliferation; Cell survival; Cell viability; Chemoresistance; Chemotherapy; Chronic myeloid leukemia; Diabetes mellitus; Drug Resistance, Neoplasm; Fatty acids; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Unsaturated - pharmacology; Gene expression; Glucose; Glucose - pharmacology; Histology; Humans; Hyperglycemia; Imatinib; Inflammation; Iron; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myeloid; Life Sciences; Morphology; Myeloid leukemia; Original Article; Oxidative Stress; Polyunsaturated fatty acids; RNA, Messenger; S phase; Tumor Suppressor Protein p53 - genetics
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-023-08891-7

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.