N-3 polyunsaturated fatty acids enhanced efficacy of cytarabine in iron-overloaded NALM-6 cells via apoptotic and oxidative pathways

Abstract

Despite progress in treating acute lymphoblastic leukemia (ALL), the adverse effects of chemotherapy toxicity and iron overload from transfusions continue to affect patients' quality of life. Polyunsaturated fatty acids (PUFAs) exhibit both antitumor and anti-inflammatory properties in leukemia. This study investigated the influence of n-3 PUFA on the efficacy of cytarabine in cells with iron overload. Iron overload was induced in NALM-6 cells using ferric ammonium citrate (FAC) and quantified through atomic absorption spectroscopy (AAS). The impact of n-3 PUFA on NALM-6 cells' response to cytarabine was evaluated using MTT, lactate dehydrogenase (LDH), apoptosis, and cell cycle assays. Additionally, gene expression analyses were performed on apoptotic, anti-apoptotic, and inflammatory genes, along with oxidative stress markers such as reactive oxygen species (ROS) and malondialdehyde (MDA) levels. The administration of n-3 PUFA significantly enhanced the effectiveness of cytarabine in iron-overloaded NALM-6 cells, leading to increased LDH secretion, elevated apoptosis rates, and G1 phase cell cycle arrest. These effects were associated with the upregulation of apoptotic genes such as P53 and caspase-8, the downregulation of the anti-apoptotic gene Bcl2, and a decrease in the inflammatory gene TNF-α. Furthermore, there was a notable increase in ROS and MDA levels. Overall, n-3 PUFA treatment improved cytarabine's efficacy in iron-overloaded NALM-6 cells by activating apoptotic processes and oxidative stress pathways.