| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2113078 | Cancer Letters | 2013 | 8 Pages |
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.
► Decitabine in nanogel sustains DNMT1 depletion to overcome drug resistance. ► Decitabine-loaded nanogels are also effective in decitabine-resistant cancer cells. ► Sustained depletion of DNMT1 causes cancer cells to remain in G2/M arrest phase. ► Nanogel-loaded epigenetic drugs could potentially be explored for treating solid tumors.
