Olsalazine inhibits cell proliferation and DNA methylation in canine lymphoid tumor cell lines
Olsalazine inhibits cell proliferation and DNA methylation in canine lymphoid tumor cell lines
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DOI：
10.24425/pjvs.2021.139976
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发表时间：
2021-01-01
影响因子：
0.8
通讯作者：
Tsukamoto, A.
中科院分区：
文献类型：
--
作者：
Itoh, S.;Yamazaki, J.;Tsukamoto, A.
异常的DNA甲基化参与淋巴肿瘤的发生和发展。因此，DNA去甲基化剂是有前途的候选药物，对这些肿瘤的化疗。据报道，水杨酸衍生的抗炎剂奥沙拉嗪抑制人细胞中的DNA甲基转移酶，并具有临床上用作DNA去甲基化剂的潜力。在这项研究中，我们使用犬淋巴肿瘤细胞系（CLBL-1，GL-1和UL-1）研究了奥沙拉嗪对细胞增殖和DNA甲基化的影响。奥沙拉嗪处理导致所有三种细胞系的显著细胞生长抑制和凋亡率增加。通过酶联免疫吸附试验评估，奥沙拉嗪治疗降低了基因组DNA中5-甲基胞嘧啶的总量。全基因组DNA甲基化分析显示，1，801至5，626个CpG位点显示三种细胞系中DNA甲基化水平降低，包括ADAM 23，FES和CREB 3L 1基因的启动子区域。本研究的结果表明，DNA去甲基化剂奥沙拉嗪，抑制犬淋巴肿瘤细胞的细胞增殖和DNA甲基化，这表明它可以成为治疗犬淋巴肿瘤的候选药物。
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). Treat-ment 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.