Arsenic disulfide promoted the demethylation of in diffuse large B cell lymphoma cells.

BACKGROUND

Promoter hypermethylation of the tumor suppressor gene is one of the well-studied causes of cancer development. The drugs that reverse the process by driving demethylation could be a candidate for anticancer therapy. This study was designed to investigate the effects of arsenic disulfide on methylation in diffuse large B cell lymphoma (DLBCL).

METHODS

We knocked down the expression of in two DLBCL cell lines (, DB and SU-DHL-4 cells) using siRNA. Then the DLBCL proliferation was determined in the presence of knockdown. The methylation of in DLBCL cells was analyzed by methylation specific PCR (MSPCR). The effect of arsenic disulfide on the methylation was determined in DLBCL cell lines in the presence of different concentrations of arsenic disulfide (5 µM, 10 µM and 20 µM), respectively. To investigate the potential mechanism on the arsenic disulfide-mediated methylation, the mRNA expression of , and was determined.

RESULTS

functioned as a tumor suppressor gene in DLBCL cells, which was featured by the fact that knockdown promoted the proliferation of DLBCL cells. was found hypermethylated in DLBCL cells. Arsenic disulfide promoted the demethylation in a dose-dependent manner, which was related to the inhibition of DNMTs and the increase of MBD2.

CONCLUSION

Experimental evidence shows that functions as a tumor suppressor gene in DLBCL progression. hyper-methylation could be reversed by arsenic disulfide in a dose-dependent manner.