N-Butylpyridoquinoxaline 1, 4-dioxide alleviates experimentally induced leukemia with up-regulating sphingosine-1-phosphate receptors

Leukemia, a malignant transformation of hematopoietic cells, is one of the most prevalent types of cancer, especially in children and, globally, it was ranked 10th for cancer incidence and nineth for cancer deaths. Quinoxaline-1, 4-dioxide derivatives have been claimed to have interesting anticancer activities. This study aimed to investigate whether N-Butylpyridoquinoxaline 1, 4-Dioxide (NBPQD) has anti-leukemic effects. Leukemia was stimulated by injecting 7, 12-dimethyl benza [a] anthracene into rats that were then treated with NBPQD. NBPQD successfully restored the normal weight, and the normal total white blood cell (WBC), lymphocyte, and neutrophil counts in the leukemic rats in comparison to either the carrier rat group or the leukemic rats before treating them with NBPQD. Furthermore, NBPQD caused a 71% reduction in the percentage of blasts in the leukemic rats. Compared to the leukemic animals in which Sphingosine-1-phosphate receptor 1 (S1PR1) and Sphingosine-1-phosphate receptor 5 (S1PR5) were down-regulated, NBPQD increased mRNA expression of S1PR1 and S1PR5 in the lymphocytes of leukemic rats 9.6-and 13.3-folds, respectively. Our results indicate that NBPQD is able to alleviate leukemia and it is worthy of further characterization as a potential anti-leukemic drug. Whether up-regulation of S1PR1 and S1PR5 is involved in the mechanism of action of NBPQD needs further investigation.