Asl Misagh Mohammadi, Asl Javad Mohammadi, Naghitorabi Mojgan
Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, I.R. Iran.
Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, I.R. Iran.
Res Pharm Sci. 2021 May 12;16(3):278-285. doi: 10.4103/1735-5362.314826. eCollection 2021 Jun.
Since DNA methyltransferase enzymes play a key role in DNA methylation, they can be used as a target to alter epigenetic changes and treat cancer. Recent studies have shown that olsalazine, through its potent inhibitory effect on the DNA methyltransferase enzyme, can be a good option. The aim of this study was to investigate the effects of olsalazine on cell viability and expression of CDH1 and uPA genes in MDA-MB-231 cells compared with decitabine.
The cytotoxicity of the drugs was determined using a standard MTT assay. MDA-MB-231 cells were treated with olsalazine and decitabine with concentrations less than IC to evaluate the effect of drugs on the expression of genes. RNA was extracted from the cells after 24 and 48 h and CDH1and uPA gene expression were evaluated by quantitative real-time polymerase chain reaction method.
FINDINGS/RESULTS: The cytotoxicity of the two drugs was comparable. The IC values at 24 h were 4000 and 4500 μM for olsalazine and decitabine, respectively. The IC values of both drugs were about 300 μM at 48 h. Statistical analyzes showed a significant increase in CDH1 expression after 24-48 h treatment with olsalazine, and 48 h treatment with decitabine, without any significant increase in uPA expression.
Our results showed that olsalazine has cellular toxicity comparable to decitabine in MDA-MB-231 cells. Also compared to decitabine, olsalazine causes a greater increase in expression of CDH1 without any significant increase in uPA expression. Therefore, it appears to be a good candidate for cancer treatment.
由于DNA甲基转移酶在DNA甲基化过程中起关键作用,它们可作为改变表观遗传变化和治疗癌症的靶点。最近的研究表明,柳氮磺胺吡啶因其对DNA甲基转移酶的强大抑制作用,可能是一个不错的选择。本研究的目的是比较柳氮磺胺吡啶与地西他滨对MDA-MB-231细胞活力以及CDH1和uPA基因表达的影响。
使用标准MTT法测定药物的细胞毒性。用浓度低于半数抑制浓度(IC)的柳氮磺胺吡啶和地西他滨处理MDA-MB-231细胞,以评估药物对基因表达的影响。在24小时和48小时后从细胞中提取RNA,并用定量实时聚合酶链反应法评估CDH1和uPA基因表达。
两种药物的细胞毒性相当。柳氮磺胺吡啶和地西他滨在24小时时的半数抑制浓度分别为4000和4500μM。两种药物在48小时时的半数抑制浓度均约为300μM。统计分析表明,用柳氮磺胺吡啶处理24-48小时后以及用地西他滨处理48小时后,CDH1表达显著增加,而uPA表达没有任何显著增加。
我们的结果表明,在MDA-MB-231细胞中,柳氮磺胺吡啶具有与地西他滨相当的细胞毒性。此外,与地西他滨相比,柳氮磺胺吡啶能使CDH1表达有更大程度的增加,而uPA表达没有任何显著增加。因此,它似乎是癌症治疗的一个良好候选药物。