Efficacy of decitabine-loaded nanogels in overcoming cancer drug resistance is mediated via sustained DNA methyltransferase 1 (DNMT1) depletion.

Abstract

DNA methyltransferase 1 (DNMT1) promotes DNA methylation to maintain cancer drug resistance. The epigenetic drug, decitabine (DAC) is a potent hypomethylating agent, but its effect is transient because of its instability. We tested the efficacy of DAC-loaded nanogels in doxorubicin-resistant breast cancer cells, DAC-resistant melanoma cells, and leukemia cells. DAC in nanogel sustained DNMT1 depletion, prolonged cell arrest in the G2/M cell-cycle phase, and significantly enhanced antiproliferative effect of DAC. The efficacy of DAC-loaded nanogels was more significant in resistant than sensitive cells. Our data suggest that effective delivery of DAC and prolonged DNMT1 depletion are critical to overcoming drug resistance.

DOI: 10.1016/j.canlet.2012.12.009

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@article{Vijayaraghavalu2013EfficacyOD, title={Efficacy of decitabine-loaded nanogels in overcoming cancer drug resistance is mediated via sustained DNA methyltransferase 1 (DNMT1) depletion.}, author={Sivakumar Vijayaraghavalu and Vinod Labhasetwar}, journal={Cancer letters}, year={2013}, volume={331 1}, pages={122-9} }