The Inhibitory Effect on Tumor Cells Proliferation Induced by Arsenic Through DNMTs and its Downstream Molecules: A Systematic Review and Meta-Analysis

Abstract

Background: We aimed to systematically evaluate the regulatory effect of arsenic on DNMTs and its downstream molecules in tumor cells and to provide a theoretical framework revealing the specific mechanism of arsenic in the treatment of tumors.

Methods: Meta-analysis was performed using RevMan 5.3 and Stata 12.0, and differences between groups were described as standardized mean difference.

Results: We found out that compared with the control group, the expression of DNMT1, DNMT3a, DNMT3b, MMP-9 & β-catenin decreased and the expression of RECK and E-cadherin increased in the arsenic-treated group. Subgroup analysis showed that high-dose arsenic exposure (> 2 μmol/L) reduced the expression of DNMT1, DNMT3b, MMP-9, and β-catenin and promoted the expression of E-cadherin. Arsenic could decrease the level of DNMT1, MMP-9 & β-catenin and increase the level of E-cadherin with short-time arsenic intervention (≤ 48 h). Arsenic could reduce DNMT1, DNMT3a, DNMT3b & β-catenin in hematological tumor cells; under the effect of arsenic, the expression of DNMT1, DNMT3b, MMP-9 & β-catenin decreased in solid tumor cells. In addition, the regulation of arsenic on DNMT3a was dose-dependent in the range of arsenic concentration from 0 to 5.0 μmol/L. The dose, time, and cell types of arsenic intervention were the variables of heterogeneity.

Conclusion: Arsenic could inhibit the proliferation and viability of tumor cells, and its mechanism may be related to the reduction of DNMTs and regulation of the expression of its downstream molecules. Overall, arsenic may be a promising candidate for the treatment of tumors.

Keywords: Arsenic; DNA methylation; DNMTs; cell proliferation; meta-analysis; molecular mechanism; treatment; tumor cells.