Effect of folate in modulating the expression of DNA methyltransferase 1 and methyl-CpG-binding protein 2 in cervical cancer cell lines

Abstract

To explore the effects of folate on the expression of DNA methyltransferase 1 (DNMT1) and methyl-CpG-binding protein 2 (MeCP2) in cervical cancer cell lines. Experimental study was carried out in vitro. Human cervical cancer cell lines, including C33A cell with HPV negative and Caski cell with HPV16 positive, were treated with different concentration of folate. The expression of DNMT1 and MeCP2 protein (by Western blot) and mRNA (by real-time PCR) were then detected in the two cell lines. It was found that supplement of folate was able to reduce the cell proliferation in C33A cell (r = 0.984, P < 0.001) and Caski cell (r = 0.978, P = 0.002), as well as induced the cell apoptosis (C33A: r = 0.989, P < 0.001; Caski: r = 0.994, P < 0.001). showed that the expression levels of DNMT1 protein (C33A: r = -0.914, P < 0.001; Caski: r = -0.859, P = 0.003) and MeCP2 protein (C33A: r = -0.830, P = 0.005; Caski: r = -0.981, P < 0.001) decreased gradually with the increase of folate concentrations, but the expression of DNMT1 and MeCP2 mRNA was not observed in Caski or C33A cell. When at the same levels of folate, the expression of DNMT1 protein or mRNA was higher in Caski cell than in C33A cell. However, the expression of MeCP2 protein or mRNA was higher in C33A cell than in Caski cell. Our finding indicated that adequate folate could effectively inhibit the proliferation of cervical cancer cells and facilitate their apoptosis in vitro, thus would reverse the aberration protein expression of DNMT1 and MeCP2. That there might be a synergistic action between HPV16 infection and parafunction of DNMT1 in cervical cancer, being noticed.