N-3 PUFAs Enhancing Chemotherapy Efficacy in Acute Myeloid Leukemia While Safeguarding Healthy Cells

Acute myeloid leukemia (AML) is a rapidly progressing blood cancer with poor survival rates, necessitating aggressive treatment strategies like chemotherapy. Doxorubicin (DOXO) is commonly used but is limited by severe side effects, including myeloablation, which involves the depletion of bone marrow cells leading to immunosuppression and heightened infection risk. This study explores the potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs), specifically docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), to enhance the efficacy of DOXO against AML cells while mitigating some of its toxicities. The results show that DHA and EPA increase the DOXO-induced apoptosis in KG1a cells and greater accumulation in the sub-G1 phase, suggesting enhanced cell death. TUNEL assays confirmed increased DNA fragmentation, whereas mRNA analysis revealed upregulation of apoptosis and cell cycle regulation genes. Importantly, DHA and EPA also reduced the hemolytic activity of DOXO, suggesting a protective effect against chemotherapy-associated side effects. These findings suggest that DHA and EPA could enhance the anti-leukemic impact of DOXO, potentially reducing the need for high-dose chemotherapy and alleviating risks like myeloablation, offering a promising adjunct strategy for AML treatment.