Olsalazine inhibits cell proliferation and DNA methylation in canine lymphoid tumor cell lines

Abstract

Abnormal DNA methylation is involved in the initiation and progression of lymphoid tumors. Hence, DNA demethylating agents are promising candidate drugs for chemotherapy against these tumors. The salicylic acid derived anti-inflammatory agent, olsalazine, reportedly suppresses DNA methyltransferase in human cells and has the potential to be clinically applied as a DNA demethylating agent. In this study, we investigated the effects of olsalazine on cell proliferation and DNA methylation using canine lymphoid tumor cell lines (CLBL-1, GL-1, and UL-1). Treatment with olsalazine led to significant cell growth inhibition and increased the apoptotic rate in all three cell lines. Treatment with olsalazine reduced the total amount of 5-methylcytosine in genomic DNA, as assessed by enzyme-linked immunosorbent assay. Genome-wide analysis of DNA methylation revealed that 1,801 to 5,626 CpG sites showed decreased DNA methylation levels in three cell lines, including the promoter regions of ADAM23, FES, and CREB3L1 genes. The outcomes of the present study demonstrate that a DNA demethylating agent olsalazine, inhibits cell proliferation and DNA methylation in canine lymphoid tumor cells, suggesting that it can be a candidate drug for the treatment of lymphoid tumors in dogs.