Abstract

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 9th 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 induced in rats by 7, 12-dimethyl benza[a]anthracene (DMBA) injection and later treated with NBPQD. NBPQD successfully restored the normal weight, and the normal total WBC, lymphocyte and neutrophil counts in the leukemic rats compared to either the carrier rat group or the group of leukemic rats before applying NBPQD. Moreover, NBPQD caused a 71% decrease in the blast percentage 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.

Key words: Leukemia; N-Butylpyridoquinoxaline 1, 4-dioxide; Cytotoxicity; Sphingosine-1-phosphate receptors, gene expression