Azelaic Acid Exerts Antileukemia Effects against Acute Myeloid Leukemia by Regulating the Prdxs/ROS Signaling Pathway

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy with a poor prognosis attributed to elevated reactive oxygen species (ROS) levels. Thus, agents that inhibit ROS generation in AML should be exploited. Azelaic acid (AZA), a small molecular compound, can scavenge ROS and other free radicals, exerting antitumor effects on various tumor cells. Herein, this study evaluated the antileukemic activity of AZA against AML via regulation of the ROS signaling pathway. We found that AZA reduced intracellular ROS levels and increased total antioxidant capacity in AML cell lines and AML patient cells. AZA suppressed the proliferation of AML cell lines and AML patient cells, expending minimal cytotoxicity on healthy cells. Laser confocal microscopy showed that AZA-treated AML cells surged and ruptured gradually on microfluidic chips. Additionally, AZA promoted AML cell apoptosis and arrested the cell cycle at the G1 phase. Further analysis demonstrated that peroxiredoxin (Prdx) 2 and Prdx3 were upregulated in AZA-treated AML cells. In vivo, AZA prolonged survival and attenuated AML by decreasing CD33+ immunophenotyping in the bone marrow of a patient-derived xenograft AML model. Furthermore, mice in the AZA-treated group had an increased antioxidant capacity and Prdx2/Prdx3 upregulation. The findings indicate that AZA may be a potential agent against AML by regulating the Prdxs/ROS signaling pathway.

Untargeted Metabolomics of Korean Fermented Brown Rice Using UHPLC Q-TOF MS/MS Reveal an Abundance of Potential Dietary Antioxidative and Stress-Reducing Compounds

“…Heat map analysis was used for separating fatty acids based on different concentration, represented from blue to green in decreasing order (Figure 5A). Fatty acids like stearic acid [55], linoleic acid [56], valeric acid [57], lauric acid [58] and azelaic acid [59] were already reported in the literature as strong antioxidants and stressreducing compounds. Principal component analysis (PCA) was used to understand the correlation among different groups, and we found that the fermented brown rice sample (Ferm L. reuterii AKT1) was divergent from the other three samples.…”

Establishment of a Novel CD34+ Hematopoietic Stem Cell-Derived Xenograft Model of Hyperleukocytic Acute Myeloid Leukemia

“…In our previous reports on drug screening using a PDX model of HLL, B-NSG mice in the 2.5 Gy group survived beyond 20 days when injected with other HLL cells without malignant gene mutations [28], and B-NSG mice without irradiation survived beyond 31 days when injected with human AML cells separated from a hyperleukocytic AML-M5 patient with NPM1 and DNMT3A mutations [29]. In addition, the B-NSG mice with 1.5 Gy irradiation survived beyond 20 days when injected with human AML cells separated from a hyperleukocytic AML-M5 patient with WT1, DNMT3A and FLT3 mutations [30,31]. The mutational status of AML cells is also a key factor in immunode cient mice for the construction of a PDX model [32,33].…”

Establishment of a Novel CD34+ Hematopoietic Stem Cell-derived Xenograft Model of Hyperleukocytic Acute Myeloid Leukemia

“…In our previous reports on drug screening using a PDX model of HLL, B-NSG mice in the 2.5 Gy group survived beyond 20 days when injected with other HLL cells without malignant gene mutations [29], and B-NSG mice without irradiation survived beyond 31 days when injected with human AML cells separated from a hyperleukocytic AML-M5 patient with NPM1 and DNMT3A mutations [30]. In addition, the B-NSG mice with 1.5 Gy irradiation survived beyond 20 days when injected with human AML cells separated from a hyperleukocytic AML-M5 patient with WT1, DNMT3A and FLT3 mutations [31,32]. The mutational status of AML cells is also a key factor in immunode cient mice for the construction of a PDX model [33,34].…”