Research in Pharmaceutical Sciences (Jan 2021)
Comparison of the effects of olsalazine and decitabine on the expression of CDH1 and uPA genes and cytotoxicity in MDA-MB-231 breast cancer cells
Abstract
Background and purpose: 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. Experimental approach: 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 IC50 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 IC50 values at 24 h were 4000 and 4500 μM for olsalazine and decitabine, respectively. The IC50 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. Conclusion and implications: 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.
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