Effect of Epigenetic Drug Candidate Olsalazine on the Expression of CDH1 and uPA Genes in MCF-7 Breast Cancer Cell Line

Abstract

Background: A main epigenetic change in cancer is DNA methylation, which leads to the inactivation of tumor suppressor genes. Due to its reversible nature, many studies have focused on how to correct epigenetic imbalances via inhibiting DNA methyltransferases (DNMTs). Recent studies have shown that olsalazine can be a potent candidate for DNMT inhibition. Objectives: The current study aimed to assess the cytotoxic effect of olsalazine on MCF-7 cells and the expression of CDH1 and uPA, as cancer-related genes, compared to decitabine. Methods: The cytotoxicity of olsalazine and decitabine on MCF-7 cells was assessed by MTT assay. To evaluate the effect of drugs on the expression of CDH1 and uPA genes, MCF-7 cells were treated with olsalazine and decitabine in concentrations below their IC50 values. After 24 h, RNA of treated cells was extracted and then subjected to a quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR). Results: The MTT assay showed that olsalazine was more toxic (IC50 = 1.75 mM) in MCF-7 cells than decitabine (IC50 = 3mM). Q-RT-PCR analysis showed that olsalazine can significantly increase uPA expression along with a non-significant increase in CDH1 expression. Meanwhile, no significant change was found in gene expression after treatment with decitabine. Conclusions: This study demonstrated that olsalazine was more cytotoxic than decitabine on MCF-7 cells. Also, compared to decitabine, olsalazine could increase the expression of CDH1 and uPA genes. It suggests that olsalazine might be more potent than decitabine in inhibiting DNMTs, although further studies are needed.